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Differential Growth of Hepatoma-susceptible Liver Induced by Gene x Genome Interaction¹

The Institute for Cancer Research, 7701 Burholme Avenue, Fox Chase, Philadelphia, Pennsylvania 19111

Differences in susceptibility to spontaneous tumor formation among inbred strains of mice are well known. This inherited tumor susceptibility is expressed as a threshold characteristic, since only a strain-specific proportion of individuals of identical genotype develop the spontaneous tumor specific for that strain. Increased formation of these tumors is induced by the lethal yellow (A^y) and viable yellow (A^vy) genes. Presence of these genes also increases "normal" growth.

Spontaneous hepatoma incidence and the mean number of hepatomas per liver were greater in yellow C3H(C3H x YS) and C3H(C3H x VY) first backcross generation and yellow (C3H x YS)F₁ hybrid male mice than in the corresponding nonyellow males.

For detection of possible liver growth differences which might be related to hepatoma susceptibility, the A^y and A^vy genes, carried in the inbred YS/ChWf and VY/Wf strains, respectively, were combined with the hepatoma-susceptible C3H/HeNIcr and hepatoma-resistant C57BL/6JNIcr and BALB/cAnNIcr strain genomes as F₁ hybrids. Ratios of liver weight to body weight between 4 and 16 weeks of age were greater in the highly hepatoma-susceptible yellow C3H F₁ hybrids than among the hepatoma-resistant BALB/c and C57BL/6 F₁ hybrids. No differences in this parameter between nonyellow hepatoma-susceptible C3H and hepatoma-resistant C57BL/6 and BALB/c F₁ hybrids were found.

Age-related decreases in liver weight to body weight ratio were observed in the nonyellow F₁ hybrids, but not among the yellow F₁ hybrids.

On the basis of these and other findings, it is suggested that the basis for spontaneous hepatoma susceptibility may be found in the strain-specific metabolic pattern of the liver and that the A^y and A^vy genes affect a specific metabolic threshold involved in regulation of normal growth, as well as in hepatoma formation.

¹ This work has been supported by USPHS Grants CA-06927 and FR-05539 from the NIH and by an appropriation from the Commonwealth of Pennsylvania.

Received 12/22/69. Accepted 2/ 5/70.