METHAPYRILENE EFFECTS ON INITIATION AND PROMOTION OF GAMMA-GLUTAMYL-TRANSPEPTIDASE POSITIVE FOCI IN RAT-LIVER

  • 1 January 1982
    • journal article
    • research article
    • Vol. 35  (1) , 51-61
Abstract
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 h later were administered either methapyrilene or nitrosodiethylamine by oral gavage. The animals were promoted with 500 ppm2 phenobarbital or 200 ppm methapyrilene in drinking water for 8 wk. Fresh frozen sections of liver were then stained and scored for .gamma.-glutamyl-transpeptidase-positive foci. Methapyrilene, when tested as the nominal initiator at a single dose of 50 mg/kg or at 2 doses of 130 mg/kg and promoted by phenobarbital, did not induce foci above background levels. 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. Evidently, the carcinogenic effects of methapyrilene may be related to its ability to enhance hepatic tumorigenesis.