Methapyrilene effects on initiation and promotion of gamma-glutamyl-transpeptidase positive foci in rat liver.
The initiating and promoting effects of methapyrilene were evaluated using the hepatic enzyme-altered foci bioassay. Male Sprague-Dawley rats were partially hepatectomized and 24 hours later were administered either methapyrilene or nitrosodiethylamine by oral gavage. Subsequently, the animals were promoted with 500 ppm2 phenobarbital or 200 ppm methapyrilene in drinking water for eight weeks. Fresh frozen sections of liver were then stained and scored for gamma-glutamyl-transpeptidase (GGT)-positive foci. Methapyrilene, when tested as the nominal initiator at a single dose of 50 mg/kg or at two doses of 130 mg/kg and promoted by phenobarbital, did not induce foci above background levels. However, when substituted for phenobarbital as the promoting agent following nitrosodiethylamine initiation, methapyrilene enhanced enzyme-altered foci formation to an equal or greater extent than did the promoter phenobarbital. These results suggest that the carcinogenic effects of methapyrilene may be related to its ability to enhance hepatic tumorigenesis.
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008701:Methapyrilene / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D000631:Aminopyridines; D008701:Methapyrilene; D005723:gamma-Glutamyltransferase