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

The organochlorine pesticide 1,1'-(2,2,2-trichloroethylidene) bis(4-chlorobenzene) (DDT) and four structural analogues (bromopropylate, chlorobenzilate, dicofol and fenarimol) were investigated for their ability to inhibit gap junctional intercellular communication both in the Chinese hamster V79 metabolic co-operation assay and in the scrape-loading/dye-transfer assay in WB-F344 rat liver epithelial cells. The pesticides were also studied for their ability to enhance the development of gamma-glutamyltranspeptidase-positive altered hepatic foci and induce cytochrome P450 monooxygenase isoenzymes in nitrosamine-initiated male Sprague-Dawley rats. The in vitro studies showed all organohalogens except fenarimol to be potent inhibitors of cell-cell communication in both test systems used. Concomitant results were recorded in the in vivo study. Thus, all potent inhibitors of intercellular communication were found to enhance significantly foci development and fenarimol was again without any significant effect. All pesticides studied were shown to be potent inducers of the phenobarbital-inducible cytochrome P450b isoenzyme and to cause hepatomegaly. Thus, no strict correlation between cytochrome P450b induction/liver growth and tumour promotion-related effects in vivo and in vitro was apparent for these organohalogen pesticides in the present study.
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PMID:Promotion of altered hepatic foci development in rat liver, cytochrome P450 enzyme induction and inhibition of cell-cell communication by DDT and some structurally related organohalogen pesticides. 238 28

In this study permethrin [(3-phenoxyphenyl)-methyl-3-(2,2-dichloroethenyl)-2,2-dim ethylcyclopropanecarboxylate] and DDT [1,1-(2,2,2 trichloroethylidene)-bis-(4-chlorobenzene)] were compared in rats for their effects on early hepatic changes, proposed in the literature to be useful endpoints in screening for non-genotoxic hepatocarcinogenesis and/or liver tumour promotion. We compared the effects of both insecticides on the following endpoints: hepatomegaly, mitogenesis (DNA synthesis, mitotic activity, percentage of binuclear cells) and liver pathology. Male Wistar rats received permethrin (PERM) or DDT in one, three, five and 14 daily oral doses (at 24-h intervals) equivalent to 1/10 LD50. Distinct differences in early liver response between PERM and DDT were observed. DDT stimulated the early effect consisting of hepatomegaly accompanied by an increase in hepatocellular proliferation with signs of cell necrosis. Thus, it might be concluded, that the mitogenic effect of DDT was at least partly related to a regenerative liver response. Although PERM significantly affected DNA synthesis and increased binuclear hepatocytes, this compound did not increase the number of mitotic figures. These results suggest that PERM may inhibit of phase G2 in the cell cycle and consequently it may suppress the cell entering into the stage of mitosis (M-phase). In addition, the present findings provide evidence for the occurrence of abnormal mitoses in the hepatocytes of rats treated with DDT.
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PMID:Early hepatic changes in rats induced by permethrin in comparison with DDT. 1068 13