Hepatocarcinogenesis: a polygenic model of inherited predisposition to cancer.
The murine inbred strain C3H provides an experimental model of inherited predisposition to hepatocellular cancer. Hepatocellular neoplastic lesions induced by chemical carcinogens reach a volume 10-100-fold greater in C3H mice than in genetically resistant strains. However, the huge strain differences in tumor size are explained by relatively small differences (10%-30%) in tumor cell kinetics. Genetic linkage experiments in different crosses demonstrated that six unlinked hepatocarcinogen sensitivity (Hcs) and two hepatocarcinogen resistance (Hcr) loci determined quantitative variations in susceptibility to hepatocarcinogenesis. Such results provide the genetic basis for the strain variations in susceptibility to hepatocarcinogenesis and demonstrate a new model of polygenic inheritance of predisposition to cancer.
Dragani
T A
TA
Division of Experimental Oncology A, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Canzian
F
F
Manenti
G
G
Pierotti
M A
MA
D000818:Animals; D002872:Chromosome Deletion; D004195:Disease Models, Animal; D008040:Genetic Linkage; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics; D051379:Mice; D009154:Mutation