Failure of the peroxisome proliferator WY-14,643 to initiate growth-selectable foci in rat liver.
The ability of the peroxisome proliferator WY-14,643 to act as an initiator of hepatocarcinogenesis was examined using a modified growth-selection protocol in rats. Feeding rats 0.1% WY-14,643 in the diet for 3 weeks, coupled with partial hepatectomy after 10 days, failed to initiate the development of growth-selectable foci identifiable by 3 enzyme histochemical stains. Elevation of palmitoyl CoA oxidase activity in WY-14,643 rats from 1 to 11 days after partial hepatectomy suggested tht peroxisome proliferation, even when coupled with hepatocellular DNA replication, did not result in initiation. The failure of WY-14,643 to initiate growth-selectable foci may indicate that promotional activity is important in the hepatocarcinogenicity of the peroxisome proliferators.
Cattley
R C
RC
Chemical Industry Institute of Toxicology, Department of Experimental Pathology and Toxicology, Research Triangle Park, NC 27709.
Marsman
D S
DS
Popp
J A
JA
D000818:Animals; D002273:Carcinogens; D006498:Hepatectomy; D006861:Hydrogen Peroxide; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000502:physiology* / Q000648:ultrastructure; D010088:Oxidoreductases; D011743:Pyrimidines / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D011743:Pyrimidines; C006253:pirinixic acid; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C028427:palmitoyl CoA oxidase