Genetic susceptibility to murine hepatocarcinogenesis is associated with high growth rate of NDEA-initiated hepatocytes.
The murine hybrids (C57BL/6J X C3Hf)F1 (B6C3) and (C57BL/6J X BALB/c)F1 (B6C), which have a high and low spontaneous and induced incidence of hepatocellular tumors, respectively, were treated with a single dose of NDEA at 1 week of age followed by TCPOBOP, a phenobarbital-like promoter of liver carcinogenesis, or by vehicle, and sacrificed at 30 weeks of age. The frequency per liver of hepatocellular nodules was similar in the two hybrids. However, in male mice the mean volume of nodules was about 10-fold greater in B6C3 than in B6C mice receiving NDEA followed by vehicle, and the treatment with TCPOBOP after NDEA stimulated nodule growth, with a much greater response in B6C3 mice. In female mice no differences in the mean volume of nodules were seen between hybrids after NDEA and vehicle, whereas upon NDEA and TCPOBOP treatment the mean volume of nodules was 25-fold greater in B6C3 than in B6C females. In addition, a few hepatocellular adenomas and carcinomas were observed, mostly in animals treated with NDEA and TCPOBOP, and they were 3-fold more numerous among B6C3 than B6C mice. TCPOBOP alone induced the same biochemical and hyperplastic effects in the liver of both hybrids. Using DNA probes homologous to Moloney murine leukemia virus, intracisternal A particle and virus-like 30S sequences, no correlation was apparent between the expression of any of these endogenous retroviral families and the strain susceptibility to hepatocarcinogenesis. We hypothesize that the different susceptibility to hepatocarcinogenesis between B6C3 and B6C mice is related to a higher growth rate of B6C3 than B6C initiated liver cells.
D000236:Adenoma / Q000139:chemically induced / Q000235:genetics; D000818:Animals; D002277:Carcinoma / Q000139:chemically induced / Q000235:genetics; D004052:Diethylnitrosamine; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics; D008809:Mice, Inbred C3H / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D008815:Mice, Inbred Strains / Q000235:genetics*; D011725:Pyridines / Q000494:pharmacology
D011725:Pyridines; D004052:Diethylnitrosamine; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene