Influence of the Ay Gene on Mammary-Gland Tumors, Hepatomas, and Normal Growth in Mice

Abstract

Hybrid (C3H × Y)F₁ mice that were genetically uniform except for segregation at the agouti locus (1/2 A^yA, yellow, and 1/2 Aa, agouti) were studied in respect to body size, occurrence of mammary tumors in the females, and occurrence of hepatomas in the males. An effect of A^y increasing susceptibility to mammary tumors was noted in the age at which the tumors arose in the virgin females. The average tumor age of the Aa virgins was 15 months while that of the A^yA virgins was only 8 months. Breeding eliminated this difference, for the average tumor age in both genotypic groups of breeders was 8 months. The final incidence in all 4 groups was or approximated 100 percent. In addition to adenocarcinomas of type A or type B there was a distinct group of a type rarely seen in other strains or hybrids that has been designated as adenocarcinoma, type Y. All but one of those of this type occurred in breeders. A^y increased susceptibility to spontaneous hepatomas in the males. The incidence in both genotypic groups was high, but it was higher in the A^yA males than in the Aa males, and the A^yA males had a significantly higher average number of hepatomas than the Aa males. Males treated with CCl₄ failed to show any carcinogenic effect of this compound in increasing occurrence of hepatomas in these susceptible hybrids, and the A^y gene did not significantly increase the occurrence of hepatomas in these treated males. A^y increased body weight by approximately 10 g in the males and approximately 15 g in the females; it significantly increased total-body length in both males and females, and it significantly increased weight of gastrocnemius muscle in the females. In the combined genotypic groups of males, a significant positive correlation was found between number of spontaneous hepatomas and body weight, total-body length, and length of femur. Relationships between normal growth and neoplasia are discussed.