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.
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.
Flodström
S
S
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Hemming
H
H
Wärngård
L
L
Ahlborg
U G
UG
D000818:Animals; D001561:Benzilates / Q000633:toxicity; D002450:Cell Communication / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003634:DDT / Q000633:toxicity*; D004010:Dicofol / Q000633:toxicity; D004790:Enzyme Induction; D007306:Insecticides / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology; D011743:Pyrimidines / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D001561:Benzilates; D007306:Insecticides; D011743:Pyrimidines; C038267:isopropyl 4,4'-dibromobenzilate; D003577:Cytochrome P-450 Enzyme System; D003634:DDT; C004659:chlorobenzilate; C033789:fenarimol; D004010:Dicofol