Stage dependent enhanced induction of hepatocellular carcinomas in rats administered a second dose of diethylnitrosamine.
An experiment was performed to investigate whether the incidence of chemical carcinogen-induced liver tumors in rats is increased by administration, during promotion, of a second dose of carcinogen. Seven groups of male Fischer-344 rats were administered a dose of diethylnitrosamine (DEN), and were placed, 1 month thereafter, on a liver-tumor promotion-regimen, consisting of a choline-devoid diet containing 0.06% phenobarbital. A second dose of the carcinogen was administered, at monthly intervals of promotion, to some of the groups of animals. The experiment was terminated after 7 months of promotion, and the incidence of hepatic tumors was determined histopathologically. In rats administered the second dose of carcinogen after 2 months of promotion, the incidence of hepatocellular carcinomas was 2-3 times greater than that in the other groups of rats. The results are consistent with the proposal, advanced by others, that development of hepatocellular carcinomas may be a multi-hit process, and indicate that, after the first induced at initiation, further genomic alteration(s) may have to occur at very discrete stage(s) in the evolution of initiated cells to tumors.
Yokoyama
S
S
Lombardi
B
B
D000818:Animals; D004052:Diethylnitrosamine / Q000008:administration & dosage*; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D009367:Neoplasm Staging; D009602:Nitrosamines / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000032:analysis
D009602:Nitrosamines; D004052:Diethylnitrosamine; D005723:gamma-Glutamyltransferase