Developmental cholinotoxicants: nicotine and chlorpyrifos

Slotkin, T A

doi:10.1289/ehp.99107s171

Cited by 292Pesticide Exposure and ToxicityNicotinic Acetylcholine Receptors StudyAnesthesia and Neurotoxicity Research

Developmental cholinotoxicants: nicotine and chlorpyrifos

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Slotkin, T A·1999·Environmental Health Perspectives

DOI 10.1289/ehp.99107s171

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Abstract

The stimulation of cholinergic receptors in target cells during a critical developmental period provides signals that influence cell replication and differentiation. Accordingly, environmental agents that promote cholinergic activity evoke neurodevelopmental damage because of the inappropriate timing or intensity of stimulation. Nicotine evokes mitotic arrest in brain cells possessing high concentrations of nicotinic cholinergic receptors. In addition, the cholinergic overstimulation programs the expression of genes that evoke apoptosis and delayed cell loss. Effects of cholinesterase inhibitors exhibit many similarities to those of nicotine. Chlorpyrifos administered to developing rats in doses that do not evoke signs of overt toxicity decreased DNA synthesis and caused shortfalls in cell numbers in brain regions enriched in cholinergic innervation. In embryo cultures, chlorpyrifos also evoked apoptosis during neurulation. However, chlorpyrifos also evokes noncholinergic disruption of cell development by interfering with cell signaling via adenylyl cyclase, leading to widespread disruption that is not limited to cholinergic systems. We have tested this hypothesis in vitro with PC12 cells, which lack the enzymes necessary to produce chlorpyrifos oxon, the metabolite that inhibits cholinesterase. Chlorpyrifos inhibited DNA synthesis in undifferentiated PC12 cells, which have relatively few cholinergic receptors. Furthermore, chlorpyrifos was more effective than nicotine and its effects were not blocked by cholinergic antagonists. When cells were allowed to differentiate in the presence of chlorpyrifos, cell replication was inhibited even more profoundly and cell acquisition was arrested. At higher concentrations, chlorpyrifos also inhibited neuritic outgrowth. Thus, chlorpyrifos elicits damage by both noncholinergic and cholinergic mechanisms extending from early stages of neural cell replication through late stages of axonogenesis and terminal differentiation. Accordingly, the window of developmental vulnerability to chlorpyrifos is likely to extend from the embryonic period into postnatal life.

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Prenatal nicotine exposure in rats at plasma levels comparable to human active smokers causes apoptosis, fewer neuronal cells, truncated axonogenesis, and deficient synaptogenesis.
“In developing rats exposed prenatally to nicotine at plasma levels comparable to those in human active smokers, standard biomarkers of cell injury indicate apoptosis, reductions in the numbers of neuronal cells, truncation of axonogenesis, and deficient synaptogenesis.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [57]
Neuronal damage and cell loss involving apoptosis genes intensify after birth even after nicotine exposure stops.
“Neuronal damage and cell loss involving the activation of genes associated with apoptosis intensify in the postnatal period despite the discontinuation of nicotine exposure.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [57]
Animal models show that prenatal nicotine exposure reproduces the brain and behavior effects seen with maternal smoking in pregnancy.
“Animal models of prenatal nicotine exposure have successfully recapitulated the neurodevelopmental and behavioral phenotypes associated with maternal cigarette smoking during pregnancy,(55-57, 64, 306)”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [57]
Chlorpyrifos overstimulates cholinergic receptors in a way similar to nicotine.
“chlorpyrifos, an acetylcholinesterase inhibitor and widely-used organophosphate insecticide that leads to inappropriate overstimulation of cholinergic receptors similar to that caused by nicotine.(57)”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [57]

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Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.
Greene, L., & Tischler, A. S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.7.2424 · Cited by 5,594 · see citing works
Fetal Nicotine or Cocaine Exposure: Which One is Worse?
Slotkin, T. A. (1998) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37495-6 · Cited by 676 · see citing works
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In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides
Bagchi, D. (1995) · Toxicology · doi:10.1016/0300-483x(95)03156-a · Cited by 664 · see citing works
Smoking in Pregnancy and Subsequent Child Development
Butler, N. R., & Goldstein, H. (1973) · BMJ · doi:10.1136/bmj.4.5892.573 · Cited by 449 · see citing works
Fos: An immediate‐early transcription factor in neurons
Curran, T., & Morgan, J. I. (1995) · Journal of Neurobiology · doi:10.1002/neu.480260312 · Cited by 377 · see citing works
Effect of Maternal Cigarette Smoking on Pregnancy Complications and Sudden Infant Death Syndrome
DiFranza, J. R., & Lew, R. (1995) · European Journal of General Practice · doi:10.3109/13814789509160303 · Cited by 354 · see citing works
Accumulation of Chlorpyrifos on Residential Surfaces and Toys Accessible to Children
Gurunathan, S., Robson, M. G., Freeman, N., Buckley, B., Roy, A., Meyer, R., Bukowski, J. A., & Lioy, P. J. (1998) · Environmental Health Perspectives · doi:10.1289/ehp.981069 · Cited by 280 · see citing works
Developmental Neurotoxicity of Chlorpyrifos: Cellular Mechanisms
Whitney, K. D., Seidler, F. J., & Slotkin, T. A. (1995) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1995.1168 · Cited by 279 · see citing works
Self-citation
Prenatal adverse effects of nicotine on the developing brain
LICHTENSTEIGER, W., Ribary, U., Schlumpf, M., Odermatt, B., & Widmer, H. R. (1988) · Progress in brain research · doi:10.1016/s0079-6123(08)60502-6 · Cited by 263 · see citing works
Neuronal acetylcholine receptors that bind alpha-bungarotoxin mediate neurite retraction in a calcium-dependent manner
Pugh, P., & Berg, D. K. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-02-00889.1994 · Cited by 252 · see citing works
Cellular Mechanisms for Developmental Toxicity of Chlorpyrifos: Targeting the Adenylyl Cyclase Signaling Cascade
Song, X., Seidler, F. J., Saleh, J. L., Zhang, J., Padilla, S., & Slotkin, T. A. (1997) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1997.8171 · Cited by 248 · see citing works
Self-citation
Comparison of in vivo cholinesterase inhibition in neonatal and adult rats by three organophosphorothioate insecticides
Pope, C., Chakraborti, T. K., Chapman, M., Farrar, J. D., & Arthun, D. (1991) · Toxicology · doi:10.1016/0300-483x(91)90061-5 · Cited by 242 · see citing works
Nicotine administration to rats: Methodological considerations
Murrin, L. C., Ferrer, J. R., Zeng, W., & Haley, N. J. (1987) · Life Sciences · doi:10.1016/0024-3205(87)90020-8 · Cited by 237 · see citing works
Nerve growth factor-induced process formation by cultured rat pheochromocytoma cells
Tischler, A. S., & Greene, L. A. (1975) · Nature · doi:10.1038/258341a0 · Cited by 232 · see citing works
Mental development of children whose mothers smoked during pregnancy.
Naeye, R. L., & Peters, E. C. (1984) · PubMed · Cited by 227 · see citing works
Role of serotonin and other neurotransmitter receptors in brain development: basis for developmental pharmacology
Whitaker-Azmitia, P. M. (1991) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06668-2 · Cited by 226 · see citing works
Potential exposure and health risks of infants following indoor residential pesticide applications.
Fenske, R. A., Black, K., Elkner, K. P., Lee, C. L., Methner, M. M., & Soto, R. C. (1990) · American Journal of Public Health · doi:10.2105/ajph.80.6.689 · Cited by 208 · see citing works
Effects of prenatal nicotine exposure on development of central and peripheral cholinergic neurotransmitter systems. Evidence for cholinergic trophic influences in developing brain.
Navarro, H. A., Seidler, F. J., Eylers, J. P., Baker, F. E., Dobbins, S. S., Lappi, S. E., & Ta, S. (1989) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21095-3 · Cited by 198 · see citing works
Neonatal lesions of the basal forebrain cholinergic neurons result in abnormal cortical development
Höhmann, C. F., Brooks, A. R., & Coyle, J. T. (1988) · Developmental Brain Research · doi:10.1016/0165-3806(88)90244-1 · Cited by 193 · see citing works
Nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via α7-neuronal receptors and neuronal CNS receptors
Kaneko, S., Maeda, T., Kume, T., Kochiyama, H., Akaike, A., Shimohama, S., & Kimura, J. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00556-8 · Cited by 193 · see citing works
Development of [3H]nicotine binding sites in brain regions of rats exposed to nicotine prenatally via maternal injections or infusions.
Slotkin, T. A., Orband-Miller, L., & Queen, K. L. (1987) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39058-0 · Cited by 183 · see citing works
Self-citation
EFFECTS OF MATERNAL CIGARETTE SMOKING ON THE FETUS AND PLACENTA
Naeye, R. L. (1978) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1978.tb15593.x · Cited by 182 · see citing works
Chlorpyrifos Interferes with Cell Development in Rat Brain Regions
Campbell, C., Seidler, F. J., & Slotkin, T. A. (1997) · Brain Research Bulletin · doi:10.1016/s0361-9230(96)00436-4 · Cited by 179 · see citing works
Self-citation
Prenatal exposure to nicotine impairs nervous system development at a dose which does not affect viability or growth
Navarro, H. A., Seidler, F. J., Schwartz, R. D., Baker, F. E., Dobbins, S. S., & Slotkin, T. A. (1989) · Brain Research Bulletin · doi:10.1016/0361-9230(89)90146-9 · Cited by 171 · see citing works
Self-citation
Effects of prenatal nicotine exposure on biochemical development of rat brain regions: maternal drug infusions via osmotic minipumps.
Slotkin, T. A., Orband‐Miller, L. A., Queen, K. L., Whitmore, W. L., & Seidler, F. J. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22572-1 · Cited by 167 · see citing works
Self-citation
Modeling the Developmental Neurotoxicity of Chlorpyrifosin Vitro:Macromolecule Synthesis in PC12 Cells
Song, X., Violin, J. D., Seidler, F. J., & Slotkin, T. A. (1998) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1998.8424 · Cited by 162 · see citing works
Self-citation
Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum.
Huff, R. A., Corcoran, J., Anderson, J. K., & Abou-Donia, M. B. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38661-1 · Cited by 162 · see citing works
Objectively measured tobacco exposure during pregnancy: neonatal effects and relation to maternal smoking
Bardy, A. H., Seppαlä, T., Lillsunde, P. M., Kataja, J. M., Koskela, P. U., Pikkarainen, J., & Hiilesmaa, V. K. (1993) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1993.tb14262.x · Cited by 162 · see citing works
Regional distribution of nicotinic receptors during prenatal development of human brain and spinal cord
Hellström-Lindahl, E., Gorbounova, O., Seiger, Å., Mousavi, M., & Nordberg, A. (1998) · Developmental Brain Research · doi:10.1016/s0165-3806(98)00046-7 · Cited by 159 · see citing works
Untitled work
(1995) · PubMed · Cited by 156 · see citing works
Drug dosage in laboratory animals: A handbook
(1966) · Food and Cosmetics Toxicology · doi:10.1016/s0015-6264(66)80455-8 · Cited by 148 · see citing works
Nicotine Evokes Cell Death in Embryonic Rat Brain during Neurulation
Roy, T. S., Andrews, J. E., Seidler, F. J., & Slotkin, T. A. (1998) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37911-x · Cited by 147 · see citing works
Self-citation
Chlorpyrifos, Parathion, and Their Oxons Bind to and Desensitize a Nicotinic Acetylcholine Receptor: Relevance to Their Toxicities
Katz, E. J., Cortes, V. I., Eldefrawi, M. E., & Eldefrawi, A. T. (1997) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1997.8201 · Cited by 140 · see citing works
Biochemical aspects of cardiac muscle differentiation. Possible control of deoxyribonucleic acid synthesis and cell differentiation by adrenergic innervation and cyclic adenosine 3':5'-monophosphate.
Claycomb, W. C. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33062-4 · Cited by 137 · see citing works
Prenatal nicotine effects on memory in rats: pharmacological and behavioral challenges
Levin, E. D., Wilkerson, A., Jones, J. P., Channelle Christopher, N., & Briggs, S. J. (1996) · Developmental Brain Research · doi:10.1016/s0165-3806(96)00144-7 · Cited by 137 · see citing works
Prenatal exposure to nicotine via maternal infusions: effects on development of catecholamine systems.
Navarro, H. A., Seidler, F. J., Whitmore, W. W., & Ta, S. (1988) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24623-7 · Cited by 137 · see citing works
Dose-related inhibition of brain and plasma cholinesterase in neonatal and adult rats following sublethal organophosphate exposures
Pope, C., & Chakraborti, T. (1992) · Toxicology · doi:10.1016/0300-483x(92)90168-e · Cited by 134 · see citing works
Prenatal nicotine exposure and cognitive performance in rats
Levin, E. D., Briggs, S. J., Christopher, N. C., & Rose, J. E. (1993) · Neurotoxicology and Teratology · doi:10.1016/0892-0362(93)90006-a · Cited by 130 · see citing works
Effects of prenatal nicotine exposure on neuronal development: Selective actions on central and peripheral catecholaminergic pathways
Slotkin, T. A., Cho, H., & Whitmore, W. L. (1987) · Brain Research Bulletin · doi:10.1016/0361-9230(87)90130-4 · Cited by 124 · see citing works
Self-citation
Chlorpyrifos elicits mitotic abnormalities and apoptosis in neuroepithelium of cultured rat embryos
Roy, T. S., Andrews, J. E., Seidler, F. J., & Slotkin, T. A. (1998) · Teratology · doi:10.1002/(sici)1096-9926(199808)58:2 · Cited by 123 · see citing works
Self-citation
Developmental neurotoxicity of chlorpyrifos: delayed targeting of DNA synthesis after repeated administration
Dam, K., Seidler, F. J., & Slotkin, T. A. (1998) · Developmental Brain Research · doi:10.1016/s0165-3806(98)00028-5 · Cited by 121 · see citing works
Self-citation
Effects of acute and chronic prenatal nicotine treatment on central catecholamine systems of male and female rat fetuses and offspring.
Ribary, U., & LICHTENSTEIGER, W. (1989) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)23772-7 · Cited by 121 · see citing works
[3H]acetylcholine and [3H](-)nicotine label the same recognition site in rat brain.
Martino-Barrows, A. M., & Kellar, K. J. (1987) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10350-7 · Cited by 115 · see citing works
Chronic nicotine treatment counteracts the disappearance of tyrosine-hydroxylase-immunoreactive nerve cell bodies, dendrites and terminals in the mesostriatal dopamine system of the male rat after partial hemitransection
Janson, A. M., Fuxé, K., Agnati, L. F., Kitayama, I. T., Härfstrand, A., Andersson, K., & Goldstein, M. (1988) · Brain Research · doi:10.1016/0006-8993(88)90092-3 · Cited by 114 · see citing works
Comparative neurochemical and neurobehavioral effects of repeated chlorpyrifos exposures in young and adult rats
Chakraborti, T. K., Farrar, J. D., & Pope, C. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90344-s · Cited by 113 · see citing works
The rôle of neurohumours in early embryogenesis. : I. Serotonin content of developing embryos of sea urchin and loach
Buznikov, G. A., Chudakova, I. V., & Zvezdina, N. D. (1964) · Development · doi:10.1242/dev.12.4.563 · Cited by 105 · see citing works
Organophosphorus compounds preferentially affect second messenger systems coupled to M2/M4 receptors in rat frontal cortex
Ward, T. R., & Mundy, W. R. (1996) · Brain Research Bulletin · doi:10.1016/0361-9230(95)02044-6 · Cited by 104 · see citing works
In vitro and in vivo induction of heat shock (stress) protein (Hsp) gene expression by selected pesticides
Bagchi, D., Bhattacharya, G., & STOHS, S. J. (1996) · Toxicology · doi:10.1016/0300-483x(96)03350-1 · Cited by 102 · see citing works
Inhibition of DNA synthesis in neonatal rat brain regions caused by acute nicotine administration
McFarland, B. J., Seidler, F. J., & Slotkin, T. A. (1991) · Developmental Brain Research · doi:10.1016/0165-3806(91)90008-7 · Cited by 100 · see citing works
Self-citation
Effects of maternal nicotine injections on brain development in the rat: Ornithine decarboxylase activity, nucleic acids and proteins in discrete brain regions
Slotkin, T. A., Greer, N. L., Faust, J. B., Cho, H., & Seidler, F. J. (1986) · Brain Research Bulletin · doi:10.1016/0361-9230(86)90159-0 · Cited by 99 · see citing works
Self-citation
Fetal growth retardation in rats from different levels of hypoxia
de Grauw, T. J., Myers, R. E., & Scott, W. J. (2009) · Biology of the Neonate · doi:10.1159/000242515 · Cited by 98 · see citing works
Effect of maternal nicotine on the development of sites for [<sup>3</sup>H]nicotine binding in the fetal brain
Hagino, N., & Lee, J. W. (1985) · International Journal of Developmental Neuroscience · doi:10.1016/0736-5748(85)90046-2 · Cited by 98 · see citing works
The role of neurohumours in early embryogenesis
Buznikov, G. A., Кост, А. Н., Kucherova, N. F., Mndzhoyan, A. L., Suvorov, N. N., & Berdysheva, L. V. (1970) · Development · doi:10.1242/dev.23.3.549 · Cited by 97 · see citing works
Perinatal and Neonatal Issues of Substance Abuse
Bell, G. L., & Lau, K. K. (1995) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(16)38946-5 · Cited by 97 · see citing works
Prenatal nicotine affects fetal testosterone and sexual dimorphism of saccharin preference
LICHTENSTEIGER, W., & Schlumpf, M. (1985) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(85)90018-8 · Cited by 96 · see citing works
Nutrition and the developing nervous system
Dodge, P. R., Prensky, A. L., & Feigin, R. D. (1975) · Mosby eBooks · Cited by 95 · see citing works
Prenatal cocaine and/or nicotine exposure in rats: Preliminary findings on long-term cognitive outcome and genital development at birth
Cutler, A. (1996) · Neurotoxicology and Teratology · doi:10.1016/s0892-0362(96)00125-0 · Cited by 95 · see citing works
Behavioral and neurochemical effects of acute chlorpyrifos in rats: tolerance to prolonged inhibition of cholinesterase.
Bushnell, P. J., Pope, C., & Padilla, S. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38352-7 · Cited by 94 · see citing works
Nutrition and the developing nervous system
Dobbing, J. (1976) · Neuroscience · doi:10.1016/0306-4522(76)90125-1 · Cited by 94 · see citing works
Fetal nicotine exposure ablates the ability of postnatal nicotine challenge to release norepinephrine from rat brain regions
Seidler, F. J., Levin, E. D., Lappi, S. E., & Slotkin, T. A. (1992) · Developmental Brain Research · doi:10.1016/0165-3806(92)90170-2 · Cited by 92 · see citing works
Self-citation
Biochemical aspects of cardiac muscle differentiation. Determination of deoxyribonucleic acid template availability and 3′-hydroxyl termini in nuclei and chromatin by using exogenous deoxyribonucleic acid polymerases
Claycomb, W. C. (1978) · Biochemical Journal · doi:10.1042/bj1710289 · Cited by 91 · see citing works
Prenatal Exposure to Nicotine: What Can We Learn from Animal Models?
Slotkin, T. A. (1992) · Elsevier eBooks · doi:10.1016/b978-0-08-092667-4.50010-6 · Cited by 91 · see citing works
Self-citation
Deficits in development of central cholinergic pathways caused by fetal nicotine exposure: Differential effects on choline acetyltransferase activity and [3H]hemicholinium-3 binding
Zahalka, E. A., Seidler, F. J., Lappi, S. E., McCook, E. C., Yanai, J., & Slotkin, T. A. (1992) · Neurotoxicology and Teratology · doi:10.1016/0892-0362(92)90047-e · Cited by 90 · see citing works
Self-citation
Early Biochemical Detection of Delayed Neurotoxicity Resulting from Developmental Exposure to Chlorpyrifos
Johnson, D., Seidler, F. J., & Slotkin, T. A. (1998) · Brain Research Bulletin · doi:10.1016/s0361-9230(97)00329-8 · Cited by 83 · see citing works
Self-citation
Adenosine 3',5'-Monophosphate Concentrations and Isoproterenol-Induced Synthesis of Deoxyribonucleic Acid in Mouse Parotid Gland
Guidotti, A., Weiss, B., & Costa, E. (1972) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)12775-2 · Cited by 82 · see citing works
Regulation of acetylcholinesterase activity by nerve growth factor. Role of transcription and dissociation from effects on proliferation and neurite outgrowth.
Greene, L., & Rukenstein, A. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69172-6 · Cited by 80 · see citing works
Prenatal nicotine exposure impairs β-adrenergic function: Persistent chronotropic subsensitivity despite recovery from deficits in receptor binding
Navarro, H. A., Mills, E., Seidler, F. J., Baker, F. E., Lappi, S. E., Tayyeb, M. I., Spencer, J. R., & Slotkin, T. A. (1990) · Brain Research Bulletin · doi:10.1016/0361-9230(90)90066-9 · Cited by 76 · see citing works
Self-citation
Cryptic brain cell injury caused by fetal nicotine exposure is associated with persistent elevations of c-fos protooncogene expression1Supported by a grant from the Smokeles Tobacco Research Council.1
Slotkin, T. A., McCook, E. C., & Seidler, F. J. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01345-5 · Cited by 74 · see citing works
Self-citation
[3H](-)nicotine binding sites in fetal human brain
Cairns, N. J., & Wonnacott, S. (1988) · Brain Research · doi:10.1016/0006-8993(88)90192-8 · Cited by 73 · see citing works
The effects of maternal nicotine absorption or hypoxic episodes upon appetitive behavior of rat offspring
Martin, J. C., & Becker, R. (1971) · Developmental Psychobiology · doi:10.1002/dev.420040205 · Cited by 72 · see citing works
Nicotine rescues PC12 cells from death induced by nerve growth factor deprivation
Yamashita, H., & Nakamura, S. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12829-9 · Cited by 70 · see citing works
Effects of acute hypoxia on neonatal rat brain: Regionally selective, long-term alterations in catecholamine levels and turnover
Seidler, F. J., & Slotkin, T. A. (1990) · Brain Research Bulletin · doi:10.1016/0361-9230(90)90200-j · Cited by 65 · see citing works
Self-citation
Perinatal Effects of Nicotine
Nasrat, H. A., Al‐Hachim, G. M., & Mahmood, F. A. (2009) · Biology of the Neonate · doi:10.1159/000242503 · Cited by 63 · see citing works
In vitro effect of chlorpyrifos oxon on muscarinic receptors and adenylate cyclase.
Ra, H., & Mb, A.-D. (1995) · PubMed · Cited by 62 · see citing works
Biochemical determinants of growth sparing during neonatal nutritional deprivation or enhancement: ornithine decarboxylase, polyamines, and macromolecules in brain regions and heart
Bell, J. M., Whitmore, W. L., Queen, K. L., Orband-Miller, L., & Slotkin, T. A. (1987) · Pediatric Research · doi:10.1203/00006450-198711000-00024 · Cited by 53 · see citing works
Self-citation
Efferent and Afferent Connections of Mouse Sensory-Motor Cortex Following Cholinergic Deafferentation at Birth
Höhmann, C. F., Wilson, L. E., & Coyle, J. T. (1991) · Cerebral Cortex · doi:10.1093/cercor/1.2.158 · Cited by 52 · see citing works
Chlorpyrifos: Assessment of Potential for Delayed Neurotoxicity by Repeated Dosing in Adult Hens with Monitoring of Brain Acetylcholinesterase, Brain and Lymphocyte Neurotoxic Esterase, and Plasma Butyrylcholinesterase Activities
Richardson, R. J. (1993) · Fundamental and Applied Toxicology · doi:10.1006/faat.1993.1076 · Cited by 52 · see citing works
The effects of nicotine administration in utero upon activity in the rat
Martin, J. C., & Becker, R. (1970) · Psychonomic Science · doi:10.3758/bf03335507 · Cited by 51 · see citing works
Rapid arrest of DNA synthesis by N 6 ,O 2' -dibutyryl cyclic adenosine 3',5'-monophosphate in cultured hepatoma cells.
Wijk, R. V., Wicks, W. D., Bevers, M. M., et al. (1973) · PubMed · Cited by 51 · see citing works
Inducible Proto-oncogene Transcription Factors: Third Messengers in the Brain?Preprint
Curran, T., Abate-Shen, C. T., Cohén, D., et al. (1990) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1990.055.01.024 · Cited by 49 · see citing works
Roles for neurotransmitters in development: possible interaction with drugs during the fetal and neonatal periods.
Jm, L. (1985) · PubMed · Cited by 48 · see citing works
Effects of neonatal hypoxia on brain development in the rat: immediate and long-term biochemical alterations in discrete regions
Slotkin, T. A., Cowdery, T., Orband, L., Pachman, S., & Whitmore, W. L. (1986) · Brain Research · doi:10.1016/0006-8993(86)90395-1 · Cited by 46 · see citing works
Self-citation
Developmental regulation of adult cortical morphology and behavior: An animal model for mental retardation
Bachman, E. S., Berger-Sweeney, J. E., Coyle, J. T., & Höhmann, C. F. (1994) · International Journal of Developmental Neuroscience · doi:10.1016/0736-5748(94)90071-x · Cited by 45 · see citing works
Modulation of cholinergic locus expression by glucocorticoids and retinoic acid is cell‐type specific
Berse, B., & Blusztajn, J. K. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00568-1 · Cited by 45 · see citing works
Fetal nicotine exposure produces postnatal up-regulation of adenylate cyclase activity in peripheral tissues
Slotkin, T. A., Navarro, H. A., McCook, E. C., & Seidler, F. J. (1990) · Life Sciences · doi:10.1016/0024-3205(90)90185-t · Cited by 45 · see citing works
Self-citation
Evaluation of the genotoxic and embryotoxic potential of chlorpyrifos and its metabolites in vivo and in vitro
Muscarella, D. E., Keown, J. F., & Bloom, S. E. (1984) · Environmental Mutagenesis · doi:10.1002/em.2860060103 · Cited by 44 · see citing works
Fetal nicotine exposure alters ontogeny of M1-receptors and their link to G-proteins
Zahalka, E. A., Seidler, F. J., Yanai, J., & Slotkin, T. A. (1993) · Neurotoxicology and Teratology · doi:10.1016/0892-0362(93)90069-z · Cited by 43 · see citing works
Self-citation
Altered development of basal and forskolin-stimulated adenylate cyclase activity in brain regions of rats exposed to nicotine prenatally
Slotkin, T. A., McCook, E. C., Lappi, S. E., & Seidler, F. J. (1992) · Developmental Brain Research · doi:10.1016/0165-3806(92)90065-5 · Cited by 41 · see citing works
Self-citation
Regional [3H]acetylcholine and [3H]nicotine binding in developing mouse brain
Larsson, C. U., Nordberg, A. K., Falkeborn, Y., & Lundberg, P. (1985) · International Journal of Developmental Neuroscience · doi:10.1016/0736-5748(85)90057-7 · Cited by 39 · see citing works
Cognitive and behavioral abnormalities in children whose mothers smoked cigarettes during pregnancy.
Naeye, R. L. (1992) · PubMed · Cited by 39 · see citing works
Postnatal developmental regulation of neuronal nicotinic receptor subunit α7 and multiple α4 and β2 mRNA species in the rat
Shacka, J. J., & Robinson, S. E. (1998) · Developmental Brain Research · doi:10.1016/s0165-3806(98)00058-3 · Cited by 38 · see citing works
Transcription factors in early development of the central nervous system
Scotting, P. J., & Rex, M. (1996) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1996.tb01118.x · Cited by 33 · see citing works
Mammalian PC‐12 cell genetically engineered for human cytochrome P450 2E1 expression
Mapoles, J. E., Berthou, F., Alexander, A. A., et al. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb17975.x · Cited by 30 · see citing works
Does concurrent or prior nicotine exposure interact with neonatal hypoxia to produce cardiac cell damage?
Tolson, C. M., Seidler, F. J., McCook, E. C., & Slotkin, T. A. (1995) · Teratology · doi:10.1002/tera.1420520508 · Cited by 29 · see citing works
Self-citation
Accumulation of Chlorpyrifos on Residential Surfaces and Toys Accessible to Children
Gurunathan, S., Robson, M. E., Freeman, N. C. G., et al. (1998) · Environmental Health Perspectives · doi:10.2307/3433627 · Cited by 28 · see citing works
Cell proliferation in growing cultures of dissociated embryonic mouse brain: macromolecule and ornithine decarboxylase synthesis and regulation by hormones and drugs
Bhat, N. R., Shanker, G., & Pieringer, R. A. (1983) · Journal of Neuroscience Research · doi:10.1002/jnr.490100210 · Cited by 26 · see citing works
Effects of neonatal nicotine administration on the postnatal development of central noradrenaline neurons.
JONSSON, G., & Hallman, H. (1980) · PubMed · Cited by 26 · see citing works
Chronic nicotine treatment eliminates asymmetry in striatal glucose utilization following unilateral transection of the mesostriatal dopamine pathway in rats
Owman, C., Fuxé, K., Janson, A. M., & Kåhrström, J. (1989) · Neuroscience Letters · doi:10.1016/0304-3940(89)90092-x · Cited by 24 · see citing works
Effects of chlorpyrifos on neuronal development in rat embryo midbrain micromass cultures.
Me, C., & Bidanset, J. H. (1995) · PubMed · Cited by 24 · see citing works
Effects of fetal nicotine exposure on development of adrenergic receptor binding in rat brain regions: selective changes in a1-receptors
Seidler, F. J., Lappi, S. E., Tayyeb, M. I., Ta, S., & Navarro, H. A. (1989) · Research communications in substance abuse · Cited by 24 · see citing works
Cognitive and Behavioral Abnormalities in Children Whose Mothers Smoked Cigarettes during Pregnancy
&NA; (1992) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/00004703-199212000-00007 · Cited by 22 · see citing works
Fetal Dexamethasone Exposure Affects Basal Ornithine Decarboxylase Activity in Developing Rat Brain Regions and Alters Acute Responses to Hypoxia and Maternal Separation
Carlos, R. Q., Seidler, F. J., Lappi, S. E., & Slotkin, T. A. (2009) · Biology of the Neonate · doi:10.1159/000243325 · Cited by 21 · see citing works
Self-citation
Acute stimulation of ornithine decarboxylase in neonatal rat brain regions by nicotine: a central receptor-mediated process?
Smith, W. T., Seidler, F. J., & Slotkin, T. A. (1991) · Developmental Brain Research · doi:10.1016/0165-3806(91)90069-u · Cited by 21 · see citing works
Self-citation
Cyclic AMP, Early Response Gene Expression, and DNA Synthesis in Rat Smooth Muscle Cells
Hultgårdh‐Nilsson, A., Querol‐Ferrer, V., Jonzon, B., et al. (1994) · Experimental Cell Research · doi:10.1006/excr.1994.1261 · Cited by 20 · see citing works
Cigarette Smoking and the Fetus and Child
Dunn, H. G., & McBurney, A. K. (1977) · PEDIATRICS · doi:10.1542/peds.60.5.772 · Cited by 19 · see citing works
Effects of a commercial soy lecithin preparation on development of sensorimotor behavior and brain biochemistry in the rat
Bell, J. M., & Lundberg, P. K. (1985) · Developmental Psychobiology · doi:10.1002/dev.420180105 · Cited by 17 · see citing works
Perinatal dietary exposure to soy lecithin: Altered sensitivity to central cholinergic stimulation
Bell, J. M., Whitmore, W. L., Barnes, G. A., Seidler, F. J., & Slotkin, T. A. (1986) · International Journal of Developmental Neuroscience · doi:10.1016/0736-5748(86)90001-8 · Cited by 12 · see citing works
Self-citation
[Pharmacological modifications of neuroendocrine ontogenesis. Development of receptors, nicotine and catecholamines].
LICHTENSTEIGER, W., Schlumpf, M., & Ribary, U. (1987) · PubMed · Cited by 10 · see citing works
Chlorpyrifos: Assessment of Potential for Delayed Neurotoxicity by Repeated Dosing in Adult Hens with Monitoring of Brain Acetylcholinesterase, Brain and Lymphocyte Neurotoxic Esterase, and Plasma Butyrylcholinesterase Activities
Richardson, R. J., MOORE, T. B., Kayyali, U. S., et al. (1993) · Toxicological Sciences · doi:10.1093/toxsci/21.1.89 · Cited by 10 · see citing works
Cytotoxic activity of acetylcholine receptor ligands
Blishchenko, E. Y., Mirkina, I. I., Mernenko, O. A., et al. (1997) · IUBMB Life · doi:10.1080/15216549700203171 · Cited by 5 · see citing works
Perinatal effects of nicotine
Nasrat, H. A. N., Al‐Hachim, G. M., & Mahmood, F. A. (1986) · Journal of Ethnopharmacology · doi:10.1016/0378-8741(86)90011-5 · Cited by 2 · see citing works

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Yanai J. Neurobehavioral Teratology. Amsterdam:Elsevier, 1984.

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Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates
Slotkin, T. A. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2003.06.001 · Cited by 544 · see citing works
Self-citation
Nicotine and the adolescent brain: insights from an animal model
Slotkin, T. (2002) · Neurotoxicology and Teratology · doi:10.1016/s0892-0362(02)00199-x · Cited by 284 · see citing works
Self-citation
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Trauth, J. A., Seidler, F. J., McCook, E. C., & Slotkin, T. A. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01994-0 · Cited by 230 · see citing works
Self-citation
Developmental Neurotoxicity of Perfluorinated Chemicals Modeled <i>in Vitro</i>
Slotkin, T. A., MacKillop, E. A., Melnick, R. L., Thayer, K. A., & Seidler, F. J. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.11253 · Cited by 225 · see citing works
Self-citation
If nicotine is a developmental neurotoxicant in animal studies, dare we recommend nicotine replacement therapy in pregnant women and adolescents?
Slotkin, T. A. (2008) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2007.09.002 · Cited by 206 · see citing works
Self-citation
Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products
England, L. J., Aagaard, K., Bloch, M., Conway, K., Cosgrove, K., Grana, R., Gould, T. J., Hatsukami, D., Jensen, F., Kandel, D., et al. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.11.013 · Cited by 181 · see citing works
Self-citation
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Self-citation
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Chen, R., Clifford, A., Lang, L., & Anstey, K. J. (2013) · Annals of Epidemiology · doi:10.1016/j.annepidem.2013.07.001 · Cited by 142 · see citing works
Effects of prenatal nicotine exposure on primate brain development and attempted amelioration with supplemental choline or vitamin c: neurotransmitter receptors, cell signaling and cell development biomarkers in fetal brain regions of rhesus monkeys
Slotkin, T. A., Seidler, F. J., Qiao, D., Aldridge, J. E., Tate, C. A., Cousins, M. M., Proskocil, B. J., Sekhon, H. S., Clark, J. A., Lupo, S. L., et al. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300544 · Cited by 101 · see citing works
Modeling adolescent nicotine exposure: effects on cholinergic systems in rat brain regions
Trauth, J. A., McCook, E. C., Seidler, F. J., & Slotkin, T. A. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02465-3 · Cited by 88 · see citing works
Self-citation
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Slotkin, T. A., Bodwell, B. E., Ryde, I. T., & Seidler, F. J. (2008) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2007.12.009 · Cited by 36 · see citing works
Self-citation
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Zugno, A. I., Oliveira, M. B., Mastella, G. A., Heylmann, A. S. A., Canever, L., Pacheco, F. D., Damazio, L. S., Citadin, S. A., de Lucca, L. A., Simões, L. R., et al. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.02.010 · Cited by 6 · see citing works

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Qiang, H. (2008) · Anhui nongye kexue
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Stolerman, I. P. (1988) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(88)90451-0 · Cited by 33 · see citing works
Exposure to nicotine enhances the behavioral stimulant effect of nicotine and increases binding of [3H]acetylcholine to nicotinic receptors
Ksir, C., Hakan, R., Hall, D. P., & Kellar, K. J. (1985) · Neuropharmacology · doi:10.1016/0028-3908(85)90058-9 · Cited by 204 · see citing works
The Effects of Chronic Nicotine Administration on Brain Nicotinic Receptor Numbers
Collins, A. C., & Marks, M. J. (1987) · Advances in behavioral biology · doi:10.1007/978-1-4613-1911-5_28 · Cited by 8 · see citing works
Subchronic treatment of rats with nicotine: Interconversion of nicotinic receptor subtypes in brain
Romanelli, L., Öhman, B., Adem, A., & Nordberg, A. K. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90577-8 · Cited by 39 · see citing works

Authors: Slotkin, T. A.
Affiliations: Duke University (US)
Corresponding author: Slotkin, T A
Venue: Environmental Health Perspectives
Publisher: American Chemical Society (ACS)
Published: 1999-02
Volume: 107
Issue: suppl 1
Pages: 71-80
ISSN: 0091-6765 (ISSN-L)
1552-9924
DOI: 10.1289/ehp.99107s171
OpenAlex: W2030842083
Cited by: 292
References: 111
Citations by year: 2024: 1 · 2023: 5 · 2022: 3 · 2021: 11 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 9 · 2014: 4 · 2013: 12 · 2012: 9
FWCI: 2.00
Type: journal article
Language: en
Open access: gold
doi.org
Licence: public-domain
Locations: Environmental Health Perspectives (publishedVersion, public-domain)
Environmental Health Perspectives (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Keywords: nicotine, chlorpyrifos, developmental neurotoxicity, cholinergic receptors, nicotinic acetylcholine receptors, cholinesterase inhibitors, apoptosis, neurulation, adenylyl cyclase signaling, PC12 cells, neurite outgrowth, cell differentiation, DNA synthesis inhibition, neurodevelopmental damage
MeSH terms: Animals, Brain, Cholinesterase Inhibitors, DNA, Chlorpyrifos, Humans, Insecticides, Nicotine, Parasympathetic Nervous System, PC12 Cells, Neurotransmitter Agents, Rats

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