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Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms.
Open accessAbstract
The exposure of cultured rat hepatocytes to mono(2-ethylhexyl)phthalate (MEHP) for 72 hr resulted in marked induction of peroxisomal enzyme activity (beta-oxidation; cyanide-insensitive palmitoyl CoA oxidase) and concomitant increases in the number of peroxisomes. Similar treatment of cultured guinea pig, marmoset, or human hepatocytes revealed little or no effect of MEHP. In order to eliminate possible confounding influences of biotransformation, the proximate peroxisome proliferator(s) derived from MEHP have been identified. Using cultured hepatocytes these agents were found to be metabolite VI [mono(2-ethyl-5-oxohexyl) phthalate] and metabolite IX [mono(2-ethyl-5-hydroxyhexyl) phthalate]. The addition of these "active" metabolites to cultured guinea pig, marmoset, or human hepatocytes again revealed little effect upon peroxisomes or related enzyme activities (peroxisomal beta-oxidation or microsomal lauric acid hydroxylation). These studies demonstrate a marked species difference in the response of hepatocytes to MEHP-elicited peroxisome proliferation. Preliminary studies have also suggested that peroxisome proliferation due to MEHP may be due to an initial biochemical lesion of fatty acid metabolism.
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Cited by
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators
Issemann, I., & Green, S. (1990) · Nature · doi:10.1038/347645a0 · Cited by 3,519
Schoonjans, K., Staels, B., & Auwerx, J. (1996) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(96)00066-5 · Cited by 1,047
Doull, J., Cattley, R., Elcombe, C., Lake, B. G., Swenberg, J., Wilkinson, C., Williams, G., & van Gemert, M. (1999) · Regulatory Toxicology and Pharmacology · doi:10.1006/rtph.1999.1296 · Cited by 337
Self-citationHuber, W. W., Grasl-kraupp, B., & Schulte-hermann, R. (1996) · Critical Reviews in Toxicology · doi:10.3109/10408449609048302 · Cited by 302
Hepatic peroxisome proliferation in rodents and its significance for humans
Bentley, P., Calder, I., Elcombe, C., Grasso, P., Stringer, D., & Wiegand, H.-J. (1993) · Food and Chemical Toxicology · doi:10.1016/0278-6915(93)90225-n · Cited by 271
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Metadata
- Authors
- Elcombe, C. R., & Mitchell, A. M.
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 1986-12
- Volume
- 70
- Pages
- 211-219
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- OpenAlex
- W2087936004
- Cited by
- 176
- References
- 0
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms. https://app.cochat.ai/papers/10.1289/ehp.8670211
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- Elcombe, C. R., & Mitchell, A. M. (1986). Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms. Environmental Health Perspectives. https://doi.org/10.1289/ehp.8670211
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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