Initiation and promotion of altered hepatic foci in female rats and inhibition of cell-cell communication by the imidazole fungicide prochloraz.
The imidazole fungicide prochloraz (1-[N-propyl-N-2-(2,4,6-trichlorophenoxy) ethyl carbamoyl] imidazole) was investigated for its ability to inhibit gap junctional intercellular communication in the scrape-loading/dye-transfer assay in IAR 20 rat liver epithelial cells and for effects on the initiation and promotion stages of hepatocarcinogenesis. Female Sprague-Dawley rats initiated with N-nitrosodiethylamine 24-hr after partial hepatectomy were administered prochloraz five days a week by oral gavage (30 or 150 mg/kg) for 10 weeks. Altered hepatic foci (AHF) were analyzed by quantitative stereology from liver sections stained for gamma-glutamyltranspeptidase (GGT) and glutathione S-transferase P (GST-P). The fungicide was also studied for its ability to initiate the development of GGT-positive AHF in rat liver. The in vitro studies showed prochloraz to be an inhibitor of cell-cell communication in the test system used. In the in vivo studies, prochloraz showed no effect on the initiation of GGT-positive foci. However, significant increases in the percentage of liver tissue occupied by GGT-positive AHF and the number of GST-P-positive AHF per cm3 in initiated animals were recorded in the low dose group. The present data suggest that prochloraz acts as a weak tumour promoter of hepatocarcinogenesis but does not initiate this process.
Kato
Y
Y
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Flodström
S
S
Wärngård
L
L
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D004052:Diethylnitrosamine / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D017629:Gap Junctions / Q000187:drug effects; D005982:Glutathione Transferase / Q000032:analysis; D007093:Imidazoles / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000032:analysis
D002273:Carcinogens; D005659:Fungicides, Industrial; D007093:Imidazoles; D004052:Diethylnitrosamine; C045362:prochloraz; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase