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PMID: 3104023 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms.

Environmental health perspectives ·Vol. 70 ·1986-12-00 ·Pages 211-9

Elcombe CR, Mitchell AM

Abstract

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.

MeSH Terms
Animals Callitrichinae Cells, Cultured Diethylhexyl Phthalate/analogs & derivatives,pharmacology Fatty Acids/metabolism Female Guinea Pigs Humans Liver/drug effects,metabolism,ultrastructure Male Microbodies/drug effects,ultrastructure Mitochondria, Liver/metabolism Phthalic Acids/pharmacology Rats Rats, Inbred Strains Species Specificity Structure-Activity Relationship
Chemicals
Fatty Acids Phthalic Acids Diethylhexyl Phthalate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Elcombe C R
Mitchell A M
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Article Info
Journal
Environmental health perspectives
Abbr.
Environ Health Perspect
ISSN
0091-6765
DOI
10.1289/ehp.8670211
Published
1986-12-00
Pages
211-9
Language
English
Region
United States
NLM ID
0330411
PMCID
PMC1474294
Subset
IM
External Links
PubMed source DOI: 10.1289/ehp.8670211 PMC Full Text View journal details
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