Genetic Changes in Gastric Lesion and Fibrosarcoma Susceptibilities.

Abstract

Evidence has been published that the gene for brown hair has mutated to dominant black several times in the descendants of mice which had been injected with methyleholanthrene for several generations. Concomitant with the production of these dominant hair color mutations there were also obtained (1) a considerable increase in susceptibility to induced fibrosarcomas, (2) an increased litter size, and (3) increased vitality. All 3 of these characteristics appear to be associated with the black mutant character, never with their brown litter mates. The evidence points toward the production of a widespread germinal change brought about by the effect of methylcholanthrene upon the germ plasm, but a point mutation at a single locus has not as yet been completely excluded. It has also been demonstrated that the gene for susceptibility to induced fibrosarcomas in mice shows linkage relationship with the gene for black hair pigmentation. The essential data of crossing over between these two genes on the brown tagged chromosome have already been obtained. A gene for susceptibility to a stomach lesion occurring primarily in the gastric mucosa of NHO mice also shows linkage relationship with the brown gene. The present paper reports the data obtained on the incidence of gastric lesions following the subcutaneous injection of methylcholanthrene in the black mutants and their litter mate brown segregates. Of the black mutants 6 descents have been continued for several generations, 3 of these descents were obtained from a brother-sister mating of two of the original black mutants, whereas the other 3 descents were descended from a backcross between one of the black mutants and its own mother of the original brown ancestry. Each of these 3 descents were made up of (a) pure breeding blacks, (b) derived pure breeding brown segregates, and (c) black heterozygous for brown. All mice were weaned at 30 days of age, mated together and injected subcutaneously in the right groin with 1 mg of methylcholanthrene dissolved in 0.1 cc of sesame oil at 60 days of age. They were examined periodically for the appearance of tumors and signs of sickness. All mice were killed when progressively growing tumors were evident or when they showed one or more signs of sickness, such as emaciation, wheezing or a ruffled appearance of the hair.