Preferential Formation of Benzo[ a ]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

Denissenko, Mikhail F.; Pao, Annie; Tang, Moon-shong; Pfeifer, Gerd P.

doi:10.1126/science.274.5286.430

Cited by 1,650Carcinogens and Genotoxicity AssessmentCancer-related Molecular PathwaysDNA Repair Mechanisms

Preferential Formation of Benzo[ a ]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

Denissenko, Mikhail F., Pao, Annie, Tang, Moon-shong, Pfeifer, Gerd P.·1996·Science

DOI 10.1126/science.274.5286.430

Open this paper in CoChat — free account

Abstract

Cigarette smoke carcinogens such as benzo[ a ]pyrene are implicated in the development of lung cancer. The distribution of benzo[ a ]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.

Integrity signals

Registry

Crossref · 10.1126/science.274.5286.430

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Benzo[a]pyrene in cigarette smoke induces genetic mutation at specific regions of DNA identical to damage evident in lung cancer cells.
“A chemical (benzo[ a ]pyrene) found in cigarette smoke induces genetic mutation at specific regions of the gene's DNA that is identical to the damage evident in lung cancer cells.”
From Mediators and Mechanisms of Change in Psychotherapy Research (2007) · cites this paper as Denissenko et al. 1996

p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018 · see citing works
Instability and decay of the primary structure of DNA
Lindahl, T. (1993) · Nature · doi:10.1038/362709a0 · Cited by 5,679 · see citing works
Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis.
Greenblatt, M. S., Bennett, W. P., Hollstein, M., & Harris, C. C. (1994) · PubMed · Cited by 3,463 · see citing works
Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,559 · see citing works
Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene
MELLON, I. (1987) · Cell · doi:10.1016/0092-8674(87)90151-6 · Cited by 1,228 · see citing works
Molecular Biology of Mutagens and Carcinogens
Singer, B. C., & Grünberger, D. (1983) · Springer eBooks · doi:10.1007/978-1-4613-3772-0 · Cited by 797 · see citing works
5-Methylcytosine as an Endogenous Mutagen in the Human LDL Receptor and p53 Genes
Rideout, W. M., Coetzee, G. A., Olumi, A. F., & Jones, P. A. (1990) · Science · doi:10.1126/science.1697983 · Cited by 640 · see citing works
Somatic point mutations in the p53 gene of human tumors and cell lines: updated compilation
Hollstein, M. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.1.141 · Cited by 499 · see citing works
Technologies for Detection of DNA Damage and Mutations
Pfeifer, G. P. (1996) · Springer eBooks · doi:10.1007/978-1-4899-0301-3 · Cited by 262 · see citing works
Self-citation
Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens.
Puisieux, A., Lim, S.-K., Groopman, J. D., & Öztürk, M. (1991) · PubMed · Cited by 260 · see citing works
NUCLEOTIDE EXCISION REPAIR
Sancar, A., & Tang, M. (1993) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1993.tb09233.x · Cited by 256 · see citing works
Self-citation
Complete and tissue-independent methylation of CpG sites in the p53 gene: implications for mutations in human cancers.
Tornaletti, S., & Pfeifer, G. P. (1995) · PubMed · Cited by 252 · see citing works
Self-citation
Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions.
Eisenstadt, E., Warren, A. J., Porter, J., Atkins, D., & Miller, J. H. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.6.1945 · Cited by 180 · see citing works
In vivo mapping of a DNA adduct at nucleotide resolution: detection of pyrimidine (6-4) pyrimidone photoproducts by ligation-mediated polymerase chain reaction.
Pfeifer, G. P., Drouin, R., Riggs, A. D., & Holmquist, G. P. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.4.1374 · Cited by 176 · see citing works
Self-citation
The distribution of UV photoproducts along the human p53 gene and its relation to mutations in skin cancer.
Tornaletti, S., Rozek, D., & Pfeifer, G. P. (1993) · PubMed · Cited by 151 · see citing works
Self-citation
Preferential repair and strand-specific repair of benzo[a]pyrene diol epoxide adducts in the HPRT gene of diploid human fibroblasts.
Chen, R., Maher, V. M., Brouwer, J., van de Putte, P., & McCormick, J. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5413 · Cited by 125 · see citing works
Effect of excision repair by diploid human fibroblasts on the kinds and locations of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene in the coding region of the HPRT gene.
Chen, R., Maher, V. M., & McCormick, J. J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8680 · Cited by 125 · see citing works
Sequence specificity of mutations induced by benzo[a]pyrene-7,8-diol-9,10-epoxide at endogenousaprt gene in CHO cells
Mazur, M., & Glickman, B. W. (1988) · Somatic Cell and Molecular Genetics · doi:10.1007/bf01534647 · Cited by 122 · see citing works
The Spectrum of Mutations at the p53 Locus
Levine, A. J., Wu, M. C., Chang, A., Silver, A., Attiyeh, E. F., Lin, J., & Epstein, C. B. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb12115.x · Cited by 105 · see citing works
Mechanism of action of the Escherichia coli UvrABC nuclease: Clues to the damage recognition problem
Houten, B. V., & Snowden, A. (1993) · BioEssays · doi:10.1002/bies.950150108 · Cited by 94 · see citing works
Carcinogen biomarkers related to smoking and upper aerodigestive tract cancer
Hecht, S. S., Carmella, S. G., Murphy, S. E., Foiles, P. G., & Chung, F. (1993) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240531005 · Cited by 60 · see citing works
DNA repair in human cells: quantitative assessment of bulky anti-BPDE-DNA adducts by non-competitive immunoassays
Venkatachalam, S., Denissenko, M. F., & Wani, A. A. (1995) · Carcinogenesis · doi:10.1093/carcin/16.9.2029 · Cited by 54 · see citing works
Self-citation
The omnipotent nucleosome
van Holde, K. (1993) · Nature · doi:10.1038/362111a0 · Cited by 45 · see citing works

Flagged first, then by citations

1 of the 24 references couldn’t be matched to a known paper.

Sorted by citations

Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
Chalmers, Z. R., Connelly, C. F., Fabrizio, D., Gay, L., Ali, S. M., Ennis, R., Schrock, A., Campbell, B., Shlien, A., Chmielecki, J., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0424-2 · Cited by 3,519 · see citing works
Cancer is a preventable disease that requires major lifestyle changes
Anand, P., Kunnumakara, A. B., Sundaram, C., Harikumar, K. B., Tharakan, S. T., Lai, O. S., Sung, B., & Aggarwal, B. B. (2008) · Pharmaceutical Research · doi:10.1007/s11095-008-9661-9 · Cited by 2,632 · see citing works
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110025 · Cited by 2,575 · see citing works
Mediators and Mechanisms of Change in Psychotherapy Research
Kazdin, A. E. (2007) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.3.022806.091432 · Cited by 2,504 · see citing works
Lung Cancer: Epidemiology, Etiology, and Prevention
Cruz, C. S. D., Tanoue, L. T., & Matthay, R. A. (2011) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2011.09.001 · Cited by 2,501 · see citing works
TP53 mutations in human cancers: origins, consequences, and clinical use.
Olivier, M., Hollstein, M., & Hainaut, P. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001008 · Cited by 2,199 · see citing works
A Comprehensive Survey of Ras Mutations in Cancer
Prior, I. A., Lewis, P. D., & Mattos, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2612 · Cited by 2,063 · see citing works
Tobacco Smoke Carcinogens and Lung Cancer
Hecht, S. S. (1999) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/91.14.1194 · Cited by 1,976 · see citing works
Formation of polycyclic aromatic hydrocarbons and their growth to soot—a review of chemical reaction pathways
Richter, H., & Howard, J. B. (2000) · Progress in Energy and Combustion Science · doi:10.1016/s0360-1285(00)00009-5 · Cited by 1,839 · see citing works
Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambient air.
Boström, C.-E., Gerde, P., Hanberg, A., Jernström, B., Johansson, C., Kyrklund, T., Rannug, A., Törnqvist, M., Victorin, K., & Westerholm, R. N. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.110-1241197 · Cited by 1,701 · see citing works
Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database
Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S. V., Hainaut, P., & Olivier, M. (2007) · Human Mutation · doi:10.1002/humu.20495 · Cited by 1,598 · see citing works
“In lung cancers, V157F, R158L, R248L, and R273L hotspots are due to G4T transversions that have been shown to be caused by the presence of benzo(a)-pyrene diol epoxide (BPDE) adducts on guanines at these codons [Denissenko et al., 1996].”
Background
Tobacco carcinogens, their biomarkers and tobacco-induced cancer
Hecht, S. S. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1190 · Cited by 1,551 · see citing works
Airborne Particulate Matter and Human Health: Toxicological Assessment and Importance of Size and Composition of Particles for Oxidative Damage and Carcinogenic Mechanisms
Valavanidis, A., Fiotakis, K., & Vlachogianni, T. (2008) · Journal of Environmental Science and Health Part C · doi:10.1080/10590500802494538 · Cited by 1,491 · see citing works
Mutations of the Epidermal Growth Factor Receptor Gene in Lung Cancer
Kosaka, T., Yatabe, Y., Endoh, H., Kuwano, H., Takahashi, T., & Mitsudomi, T. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2818 · Cited by 1,220 · see citing works
Mutational signatures associated with tobacco smoking in human cancer
Alexandrov, L. B., Ju, Y. S., Haase, K., Van Loo, P., Martincorena, I., Nik-Zainal, S., Totoki, Y., Fujimoto, A., Nakagawa, H., Shibata, T., et al. (2016) · Science · doi:10.1126/science.aag0299 · Cited by 1,100 · see citing works
Evidence-based treatment and practice: new opportunities to bridge clinical research and practice, enhance the knowledge base, and improve patient care
Kazdin, A. E. (2008) · American Psychologist · doi:10.1037/0003-066x.63.3.146 · Cited by 1,112 · see citing works
Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers
Pfeifer, G. P., Denissenko, M. F., Olivier, M., Tretyakova, N. Y., Hecht, S. S., & Hainaut, P. L. (2002) · Oncogene · doi:10.1038/sj.onc.1205803 · Cited by 1,114 · see citing works
Self-citation
The MDM2 gene amplification database
Momand, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3453 · Cited by 982 · see citing works
p53 and Human Cancer: The First Ten Thousand Mutations
Hainaut, P. L., & Hollstein, M. C. (1999) · Advances in cancer research · doi:10.1016/s0065-230x(08)60785-x · Cited by 980 · see citing works
Chemistry, Biology, and Medicine of Fluorescent Nanomaterials and Related Systems: New Insights into Biosensing, Bioimaging, Genomics, Diagnostics, and Therapy
Yao, J., Yang, M., & Duan, Y. (2014) · Chemical Reviews · doi:10.1021/cr200359p · Cited by 948 · see citing works
TP53 mutations in human cancers: Functional selection and impact on cancer prognosis and outcomes
Petitjean, A., Achatz, M. I. W., Borresen-Dale, A. L., Hainaut, P., & Olivier, M. (2007) · Oncogene · doi:10.1038/sj.onc.1210302 · Cited by 884 · see citing works
Polycyclic Aromatic Hydrocarbons: From Metabolism to Lung Cancer
Moorthy, B., Chu, C., & Carlin, D. J. (2015) · Toxicological Sciences · doi:10.1093/toxsci/kfv040 · Cited by 807 · see citing works
Delineating mechanisms of change in child and adolescent therapy: methodological issues and research recommendations
Kazdin, A. E., & Nock, M. K. (2003) · Journal of Child Psychology and Psychiatry · doi:10.1111/1469-7610.00195 · Cited by 774 · see citing works
Understanding how and why psychotherapy leads to change
Kazdin, A. E. (2009) · Psychotherapy Research · doi:10.1080/10503300802448899 · Cited by 728 · see citing works
Non–Small Cell Lung Cancer
_, _. (2008) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2008.0021 · Cited by 737 · see citing works
A Compendium of Mutational Signatures of Environmental Agents
Kucab, J. E., Zou, X., Morganella, S., Joel, M., Nanda, A. S., Nagy, E., Gomez, C., Degasperi, A., Harris, R., Jackson, S. P., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.001 · Cited by 660 · see citing works
Drug Interactions with Tobacco Smoking
Zevin, S., & Benowitz, N. L. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199936060-00004 · Cited by 702 · see citing works
Waging war on modern chronic diseases: primary prevention through exercise biology
Booth, F. W., Gordon, S. E., Carlson, C. J., & Hamilton, M. T. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.2.774 · Cited by 693 · see citing works
A Mutator Phenotype in Cancer 1
Loeb, L. A. (2001) · Cited by 670 · see citing works
Toxicities of Polycyclic Aromatic Hydrocarbons for Aquatic Animals
Honda, M., & Suzuki, N. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17041363 · Cited by 643 · see citing works
Environment and Cancer: Who Are Susceptible?
Perera, F. P. (1997) · Science · doi:10.1126/science.278.5340.1068 · Cited by 638 · see citing works
Epidemiology of Lung Cancer
Alberg, A. J., Ford, J. G., & Samet, J. M. (2007) · CHEST Journal · doi:10.1378/chest.07-1347 · Cited by 625 · see citing works
Why are there hotspot mutations in the TP53 gene in human cancers?
Baugh, E. H., Ke, H., Levine, A. J., Bonneau, R., & Chan, C. S. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.180 · Cited by 609 · see citing works
DNA methylation: past, present and future directions
Robertson, K. D., & Jones, P. A. (2000) · Carcinogenesis · doi:10.1093/carcin/21.3.461 · Cited by 609 · see citing works
Natural and Synthetic Chromenes, Fused Chromenes, and Versatility of Dihydrobenzo[h]chromenes in Organic Synthesis
Pratap, R., & Ram, V. J. (2014) · Chemical Reviews · doi:10.1021/cr500075s · Cited by 607 · see citing works
Tobacco smoke is a source of toxic reactive glycation products
Cerami, C., Founds, H., Nicholl, I. D., Mitsuhashi, T., Giordano, D., VanPatten, S., Lee, A., Al‐Abed, Y., Vlassara, H., Bucala, R., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13915 · Cited by 550 · see citing works
Composition of Air Pollution Particles and Oxidative Stress in Cells, Tissues, and Living Systems
Ghio, A. J., Carraway, M. S., & Madden, M. C. (2011) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2012.632359 · Cited by 544 · see citing works
Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention
Hecht, S. S. (2002) · The Lancet Oncology · doi:10.1016/s1470-2045(02)00815-x · Cited by 536 · see citing works
Repair of Tobacco Carcinogen-Induced DNA Adducts and Lung Cancer Risk: a Molecular Epidemiologic Study
Wei, Q. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.21.1764 · Cited by 506 · see citing works
Aristolochic acid as a probable human cancer hazard in herbal remedies: a review
Arlt, V. M. (2002) · Mutagenesis · doi:10.1093/mutage/17.4.265 · Cited by 503 · see citing works
Genotoxicity of tobacco smoke and tobacco smoke condensate: a review
DeMarini, D. M. (2004) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2004.02.001 · Cited by 493 · see citing works
Lung carcinogenesis by tobacco smoke
Hecht, S. S. (2012) · International Journal of Cancer · doi:10.1002/ijc.27816 · Cited by 482 · see citing works
Dihydrodiol dehydrogenases and polycyclic aromatic hydrocarbon activation: generation of reactive and redox active o-quinones.
Penning, T., Burczynski, M., Hung, C. F., McCoull, K. D., Palackal, N., & Tsuruda, L. (1999) · Chemical Research in Toxicology · doi:10.1021/tx980143n · Cited by 440 · see citing works
Automotive Sources of Carcinogenic Polycyclic Aromatic Hydrocarbons Associated with Particulate Matter in the Chesapeake Bay Region
Dickhut, R. M., Canuel, E. A., Gustafson, K. E., Liu, K., Arzayus, K. M., Walker, S. E., Edgecombe, G. D., Gaylor, M. O., & MacDonald, E. H. (2000) · Environmental Science & Technology · doi:10.1021/es000971e · Cited by 453 · see citing works
Clonal Genetic Alterations in the Lungs of Current and Former Smokers
Mao, L., Lee, J., Kurie, J. M., Fan, Y., Lippman, S. M., Broxson, A., Khuri, F. R., Hong, W. K., Lee, J. J., Yu, R., et al. (1997) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/89.12.857 · Cited by 447 · see citing works
Methylation matters
Costello, J., & Plass, C. (2001) · Journal of Medical Genetics · doi:10.1136/jmg.38.5.285 · Cited by 447 · see citing works
IARC Database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualisation tools
Hainaut, P. L. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.1.205 · Cited by 446 · see citing works
Understanding the human health effects of chemical mixtures.
Carpenter, D. O., Arcaro, K. F., & Spink, D. C. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.02110s125 · Cited by 425 · see citing works
Nature and nurture – lessons from chemical carcinogenesis
Luch, A. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1546 · Cited by 423 · see citing works
Molecular genetics of small cell lung carcinoma
Wistuba, I. I., Gazdar, A. F., & Minna, J. D. (2001) · Seminars in Oncology · doi:10.1016/s0093-7754(01)90072-7 · Cited by 421 · see citing works
AHR in the intestinal microenvironment: safeguarding barrier function
Stockinger, B., Shah, K., & Wincent, E. (2021) · Nature reviews: Gastroenterology & hepatology · doi:10.1038/s41575-021-00430-8 · Cited by 369 · see citing works
Inflammation and Lung Cancer: Roles of Reactive Oxygen/Nitrogen Species
Azad, N., Rojanasakul, Y., & Vallyathan, V. (2008) · Journal of Toxicology and Environmental Health, Part B · doi:10.1080/10937400701436460 · Cited by 409 · see citing works
Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair
Haradhvala, N. J., Polak, P. P., Stojanov, P., Covington, K. R., Shinbrot, E., Hess, J. M., Rheinbay, E., Kim, J., Maruvka, Y. E., Braunstein, L. Z., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.050 · Cited by 387 · see citing works
Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes.
Hussain, S. P., & Harris, C. C. (1998) · PubMed · Cited by 409 · see citing works
Smoking and reproduction: gene damage to human gametes and embryos
Zenzes, M. T. (2000) · Human Reproduction Update · doi:10.1093/humupd/6.2.122 · Cited by 396 · see citing works
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive physiology · doi:10.1002/j.2040-4603.2012.tb00425.x · Cited by 397 · see citing works
Expression of Fragile Sites Triggers Intrachromosomal Mammalian Gene Amplification and Sets Boundaries to Early Amplicons
Coquelle, A., Pipiras, E., Toledo, F., Buttin, G., & Debatisse, M. (1997) · Cell · doi:10.1016/s0092-8674(00)80201-9 · Cited by 390 · see citing works
TP53 Mutations in Nonsmall Cell Lung Cancer
Mogi, A., & Kuwano, H. (2011) · BioMed Research International · doi:10.1155/2011/583929 · Cited by 392 · see citing works
Acrolein is a major cigarette-related lung cancer agent: Preferential binding at p53 mutational hotspots and inhibition of DNA repair
Feng, Z., Hu, W., Hu, Y., & Tang, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607031103 · Cited by 374 · see citing works
Self-citation
Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors
Herceg, Z. (2007) · Mutagenesis · doi:10.1093/mutage/gel068 · Cited by 371 · see citing works
p63 Gene Mutations in EEC Syndrome, Limb-Mammary Syndrome, and Isolated Split Hand–Split Foot Malformation Suggest a Genotype-Phenotype Correlation
van Bokhoven, H., Hamel, B. C. J., Bamshad, M., Sangiorgi, E., Gurrieri, F., Duijf, P. H. G., Vanmolkot, K. R. J., van Beusekom, E., van Beersum, S. E. C., Celli, J., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/323123 · Cited by 372 · see citing works
FDG Accumulation and Tumor Biology
Pauwels, E. K. J., Ribeiro, M.-J., Stoot, J. H. M. B., McCready, V. R., Bourguignon, M., & Maziere, B. (1998) · Nuclear Medicine and Biology · doi:10.1016/s0969-8051(97)00226-6 · Cited by 368 · see citing works
Biological impact of environmental polycyclic aromatic hydrocarbons (ePAHs) as endocrine disruptors
Zhang, Y., Dong, S., Wang, H., Tao, S., & Kiyama, R. (2016) · Environmental Pollution · doi:10.1016/j.envpol.2016.03.050 · Cited by 362 · see citing works
A mutator phenotype in cancer.
Loeb, L. A. (2001) · PubMed · Cited by 349 · see citing works
Role of oxidative DNA damage in cancer initiation and promotion.
Poulsen, H. E., Priemé, H., & Loft, S. H. (1998) · PubMed · Cited by 343 · see citing works
Cytosine methylation determines hot spots of DNA damage in the human P 53 gene
Denissenko, M. F., Chen, J. X., Tang, M., & Pfeifer, G. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3893 · Cited by 339 · see citing works
Self-citation
Naphthalene?an environmental and occupational toxicant
Preuss, R., Angerer, J., & Drexler, H. (2003) · International Archives of Occupational and Environmental Health · doi:10.1007/s00420-003-0458-1 · Cited by 338 · see citing works
Formation and consumption of single-ring aromatic hydrocarbons and their precursors in premixed acetylene, ethylene and benzene flamesElectronic supplementary information (ESI) available: Thermodynamic and kinetic property data. See http://www.rsc.org/suppdata/cp/b1/b110089k/
Richter, H., & Howard, J. B. (2002) · Physical Chemistry Chemical Physics · doi:10.1039/b110089k · Cited by 332 · see citing works
The p53 Tumor Suppressor Gene: From Molecular Biology to Clinical Investigation
Soussi, T. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06705.x · Cited by 332 · see citing works
Contributions of risk-factor research to developmental psychopathology
Kazdin, A. E., Kraemer, H. C., Kessler, R. C., Kupfer, D. J., & Offord, D. R. (1997) · Clinical Psychology Review · doi:10.1016/s0272-7358(97)00012-3 · Cited by 328 · see citing works
Causality and causal inference in epidemiology: the need for a pluralistic approach
Vandenbroucke, J. P., Broadbent, A., & Pearce, N. E. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyv341 · Cited by 328 · see citing works
Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons
Sundberg, K. (1998) · Carcinogenesis · doi:10.1093/carcin/19.3.433 · Cited by 318 · see citing works
Patterns of p53 G->T transversions in lung cancers reflect the primary mutagenic signature of DNA-damage by tobacco smoke
Hainaut, P. (2001) · Carcinogenesis · doi:10.1093/carcin/22.3.367 · Cited by 375 · see citing works
Advances in Chemical Carcinogenesis: A Historical Review and Prospective
Loeb, L. A., & Harris, C. C. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2852 · Cited by 314 · see citing works
Molecular Genetics of Lung Cancer
Sekido, Y., Fong, K. M., & Minna, J. D. (2003) · Annual Review of Medicine · doi:10.1146/annurev.med.54.101601.152202 · Cited by 318 · see citing works
“IARC Group 2A Carcinogens” reported in cigarette mainstream smoke
Smith, C. J., Perfetti, T. A., Rumple, M. A., Rodgman, A., & Doolittle, D. J. (2000) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(99)00156-8 · Cited by 309 · see citing works
Targeting of Lung Cancer Mutational Hotspots by Polycyclic Aromatic Hydrocarbons
Smith, L. E., Denissenko, M. F., Bennett, W. P., Li, H., Amin, S., Tang, M., & Pfeifer, G. P. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.10.803 · Cited by 307 · see citing works
Self-citation
Epidermal growth factor receptor family in lung cancer and premalignancy
Franklin, W. A., Veve, R., Hirsch, F. R., Helfrich, B. A., & Bunn, P. A. (2002) · Seminars in Oncology · doi:10.1053/sonc.2002.31520 · Cited by 306 · see citing works
Room-Temperature Single-Nucleotide Polymorphism and Multiallele DNA Detection Using Fluorescent Nanocrystals and Microarrays
Gerion, D., Chen, F., Kannan, B., Fu, A., Parak, W. J., Chen, D. J., Majumdar, A., & Alivisatos, A. P. (2003) · Analytical Chemistry · doi:10.1021/ac034482j · Cited by 299 · see citing works
Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF- B activation through inhibition of I B kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1
Shishodia, S., Potdar, P. D., Gairola, C. G., & Aggarwal, B. B. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg078 · Cited by 292 · see citing works
Progress in understanding the molecular pathogenesis of human lung cancer
Sekido, Y., Fong, K. M., & Minna, J. D. (1998) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(98)00010-9 · Cited by 289 · see citing works
Smoke exposure, histologic type and geography‐related differences in the methylation profiles of non‐small cell lung cancer
Toyooka, S., Maruyama, R., Toyooka, K. O., McLerran, D., Feng, Z., Fukuyama, Y., Virmani, A. K., Zöchbauer‐Müller, S., Tsukuda, K., Sugio, K., et al. (2002) · International Journal of Cancer · doi:10.1002/ijc.10787 · Cited by 288 · see citing works
The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma
Hu, W. (2002) · Carcinogenesis · doi:10.1093/carcin/23.11.1781 · Cited by 287 · see citing works
Metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-diol by human cytochrome P450 1B1
Kim, J. (1998) · Carcinogenesis · doi:10.1093/carcin/19.10.1847 · Cited by 286 · see citing works
The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting
Fingerle‐Rowson, G., Petrenko, O., Metz, C. N., Forsthuber, T. G., Mitchell, R. A., Huss, R., Moll, U. M., Müller, W., & Bucala, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533295100 · Cited by 284 · see citing works
bHLH-PAS proteins in cancer
Bersten, D. C., Sullivan, A. E., Peet, D. J., & Whitelaw, M. L. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3621 · Cited by 267 · see citing works
Progress and Challenges in Selected Areas of Tobacco Carcinogenesis
Hecht, S. S. (2007) · Chemical Research in Toxicology · doi:10.1021/tx7002068 · Cited by 282 · see citing works
Cigarette smoke condensate activates nuclear transcription factor-kappaB through phosphorylation and degradation of IkappaBalpha: correlation with induction of cyclooxygenase-2
Anto, R. J. (2002) · Carcinogenesis · doi:10.1093/carcin/23.9.1511 · Cited by 278 · see citing works
Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran
Nasrollahzadeh, D., Kamangar, F., Aghcheli, K., Sotoudeh, M., Islami, F., Abnet, C. C., Shakeri, R., Pourshams, A., Marjani, H.-A., Nouraie, M. S., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604369 · Cited by 276 · see citing works
Animal models and therapeutic molecular targets of cancer: utility and limitations
Cekanova, M., & Rathore, K. (2014) · Drug Design, Development and Therapy · doi:10.2147/dddt.s49584 · Cited by 274 · see citing works
TP53 and KRAS Mutation Load and Types in Lung Cancers in Relation to Tobacco Smoke: Distinct Patterns in Never, Former, and Current Smokers
Le Calvez, F., Mukeria, A., Hunt, J. D., Kelm, O., Hung, R. J., Tanière, P., Brennan, P., Boffetta, P., Zaridze, D. G., & Hainaut, P. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0551 · Cited by 273 · see citing works
A comprehensive review of metabolic and genomic aspects of PAH-degradation
Sakshi, & Haritash, A. K. (2020) · Archives of Microbiology · doi:10.1007/s00203-020-01929-5 · Cited by 273 · see citing works
Hepatocellular Carcinoma: From Gene to Public Health
Montesano, R., Hainaut, P. L., & Wild, C. P. (1997) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/89.24.1844 · Cited by 269 · see citing works
Mutagenesis at Methylated CpG Sequences
Pfeifer, G. P. (2006) · Springer eBooks · doi:10.1007/3-540-31390-7_10 · Cited by 267 · see citing works
Self-citation
Polyaromatic hydrocarbons (PAHs) in the water environment: A review on toxicity, microbial biodegradation, systematic biological advancements, and environmental fate.
Vijayanand, M., Ramakrishnan, A., Subramanian, R., Issac, P. K., Nasr, M., Khoo, K., Rajagopal, R., Greff, B., Azelee, N. I. W., Jeon, B.-H., et al. (2023) · Environmental Research · doi:10.1016/j.envres.2023.115716 · Cited by 228 · see citing works
Air quality in North America's most populous city – overview of the MCMA-2003 campaign
Molina, L. T., Kolb, C. E., de Foy, B., Lamb, B., Brune, W. H., Jimenez, J. L., Ramos-Villegas, R., Sarmiento, J., Paramo, V. H., Cárdenas, B., et al. (2007) · Atmospheric chemistry and physics · doi:10.5194/acp-7-2447-2007 · Cited by 263 · see citing works
Synergistic mechanisms in carcinogenesis by polycyclic aromatic hydrocarbons and by tobacco smoke: a bio-historical perspective with updates
Rubin, H. (2001) · Carcinogenesis · doi:10.1093/carcin/22.12.1903 · Cited by 261 · see citing works
Molecular mechanisms of pulmonary carcinogenesis by polycyclic aromatic hydrocarbons (PAHs): Implications for human lung cancer
Stading, R. E., Gastelum, G. M., Chu, C., Jiang, W., & Moorthy, B. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.07.001 · Cited by 258 · see citing works
Genome-wide analysis of human global and transcription-coupled excision repair of UV damage at single-nucleotide resolutionPreprint
Hu, J., Adar, S., Selby, C. P., Lieb, J. D., & Sancar, A. (2015) · Genes & Development · doi:10.1101/gad.261271.115 · Cited by 249 · see citing works
Cutting out the middleman: DNA biosensors based on electrochemical oxidation
Thorp, H. H. (1998) · Trends in biotechnology · doi:10.1016/s0167-7799(97)01162-1 · Cited by 255 · see citing works

Targeting of Lung Cancer Mutational Hotspots by Polycyclic Aromatic Hydrocarbons
Smith, L. E., Denissenko, M. F., Bennett, W. P., Li, H., Amin, S., Tang, M., & Pfeifer, G. P. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.10.803 · Cited by 307 · see citing works
Self-citation
ARTICLES Targeting of Lung Cancer Mutational Hotspots by Polycyclic Aromatic Hydrocarbons
Smith, L. E., Denissenko, M. F., Bennett, W. P., Li, H., Amin, S., Tang, M., & Pfeifer, G. P. (2000)
Self-citation
Methylated CpG dinucleotides are the preferential targets for G-to-T transversion mutations induced by benzo[a]pyrene diol epoxide in mammalian cells: similarities with the p53 mutation spectrum in smoking-associated lung cancers.
Yoon, J., Smith, L. E., Feng, Z., Tang, M., Lee, C.-S., & Pfeifer, G. P. (2001) · PubMed · Cited by 161 · see citing works
Self-citation
Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens.
Puisieux, A., Lim, S.-K., Groopman, J. D., & Öztürk, M. (1991) · PubMed · Cited by 260 · see citing works
Base damage, local sequence context andTP53mutation hotspots: a molecular dynamics study of benzo[a]pyrene induced DNA distortion and mutability
Menzies, G. E., Reed, S. H., Brancale, A., & Lewis, P. D. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv910 · Cited by 20 · see citing works

Authors: Denissenko, M. F., Pao, A., Tang, M.-S., & Pfeifer, G. P.
Affiliations: Beckman Research Institute (US)
A. Pao and M.-s. Tang, M. D. Anderson Cancer Center, University of Texas, Science Park, Smithville, TX 78957, USA.
ORCID: Tang, Moon-shong
Pfeifer, Gerd P.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1996-10-18
Volume: 274
Issue: 5286
Pages: 430-432
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.274.5286.430
OpenAlex: W1976056213
Cited by: 1,650
References: 24
Citations by year: 2026: 16 · 2025: 16 · 2024: 17 · 2023: 16 · 2022: 15 · 2021: 26 · 2020: 26 · 2019: 28 · 2018: 29 · 2017: 48 · 2016: 40 · 2015: 45 · 2014: 63 · 2013: 39 · 2012: 69
FWCI: 40.80
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r01ca065652-01a1)
National Cancer Institute (CA65652)
National Institute of Environmental Health Sciences (ES03124, R01ES003124)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords: benzo[a]pyrene, benzo[a]pyrene diol epoxide, DNA adducts, p53, lung cancer, mutational hotspots, tobacco smoke carcinogens, mutation spectrum, HeLa cells, bronchial epithelial cells, guanine adducts
MeSH terms: Bronchi, Carcinogens, Cells, Cultured, Codon, Exons, Fibroblasts, HeLa Cells, Humans, Lung Neoplasms, Mutagens, Mutation, Plants, Toxic, Smoke, Nicotiana, 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide, Dinucleoside Phosphates, Genes, p53, DNA Adducts

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Preferential Formation of Benzo[ a ]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks