HEPATOCARCINOGENESIS - A POLYGENIC MODEL OF INHERITED PREDISPOSITION TO CANCER

The murine inbred strain C3H provides an experimental model of inherit ed predisposition to hepatocellular cancer. Hepatocellular neoplastic lesions induced by chemical carcinogens reach a volume 10-100-fold gre ater in C3H mice than in genetically resistant strains. However, the h uge strain differences in tumor size are explained by relatively small differences (10%-30%) in tumor cell kinetics. Genetic linkage experim ents in different crosses demonstrated that six unlinked hepatocarcino gen sensitivity (Hcs) and two hepatocarcinogen resistance (Her) loci d etermined quantitative variations in susceptibility to hepatocarcinoge nesis. Such results provide the genetic basis for the strain variation s in susceptibility to hepatocarcinogenesis and demonstrate a new mode l of polygenic inheritance of predisposition to cancer.