Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Di-n-octyl phthalate (DOP) is the straight chain isomer of di(2-ethylhexyl) phthalate (DEHP) which is a widely used plasticizer and an environmental contaminant. DEHP is a strong inducer of peroxisome proliferation in rat liver. This is significant since other compounds which are strong inducers of peroxisome proliferation have been reported to be weak carcinogens (Reddy, J.K. and Lalwani, N.D., CRC Crit. Rev. Toxicol., 12 (1983) 1). In contrast to DEHP, DOP causes little or no induction of liver peroxisomes (Mann, A.H. et al., Toxicol. Appl. Pharmacol., 77 (1985) 116, and Gray, T.J.B. et al., Toxicology, 28 (1983) 167). In the current study the ability of 1% DOP to promote the development of putative preneoplastic lesions was evaluated. The effect of feeding 0.5% DEHP as well as equimolar amounts of its 2 major metabolites, mono(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (2-EH) were also investigated. GGT+ foci were initiated in the livers of Sprague--Dawley male rats with a single dose of diethylnitrosamine (DEN) following partial hepatectomy. The control group of rats was fed a semipurified diet (Co) for 10 weeks while the experimental groups received the semipurified diet containing the respective compounds. Induction of peroxisome proliferation was monitored by carnitine acetyltransferase (CAT) levels. DOP treatment resulted in a 6-fold increase in the number of GGT+ foci (20.8 +/- 4.0 vs. 3.5 +/- 1.3; P less than 0.05). This was accompanied by no change in liver weight and only a slight increase in CAT activity when compared with control animals. In contrast to DOP, 2-EH produced essentially no effect with regard to number of foci, peroxisome proliferation or liver weight. DEHP and MEHP induced significant peroxisome proliferation and hepatomegaly but the number of foci were significantly lower than in 2-EH-treated rats. The mechanism for the promoting ability of DOP is not clear but would not appear to be related to peroxisome proliferation. Because of the close similarity of chemical structure and metabolism between DOP and DEHP, it is possible that studies to define the mechanism of DOP induced promotion might also serve to further clarify the mechanism of DEHP induced carcinogenesis.
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PMID:Di-n-octyl phthalate (DOP), a relatively ineffective peroxisome inducing straight chain isomer of the environmental contaminant di(2-ethylhexyl)phthalate (DEHP), enhances the development of putative preneoplastic lesions in rat liver. 287 11