GENETICS OF COLON CARCINOGENESIS IN MICE TREATED WITH 1,2-DIMETHYLHYDRAZINE

Abstract

Genetic analysis of colon tumor induction by symmetrical 1,2-dimethylhydrazine (DMH) was undertaken in F1, F2 and reciprocal backcross hybrids derived from a cross between 2 inbred mouse strains, the 100% susceptible ICR/Ha and completely resistant C57BL/Ha. Mice, 12-14 wk old, received 22 weekly s.c. injections of 0.35% aqueous solution of DMH buffered to pH 6.5. A dose of 15 mg/kg per mouse per week produced invasive colon adenocarcinomas in all ICR/Ha males and females (60) within 22 wk. None of the 90 C57BL/Ha mice developed DMH tumors during 44 wk of observation. Susceptibility to the carcinogen was dominant, as indicated by 100% colon tumor incidence in reciprocal ICR/Ha .times. C57BL/Ha F1 hybrids (68) and the susceptible backcross ICR/Ha .times. F1 (42). Tumor yield in F2 hybrids (94 of 120) was 78%, which is in close agreement with the 3:1 ratio expected if a single dominant DMH susceptibility gene is inherited via the F1 from the ICR/Ha grandparent. Tumor yield in resistant backcross mice of genotype C57BL/Ha .times. F1 (46 of 117) is not out of line with the anticipated 1:1 ratio in the latter type of test hybrids. Tests with 5 isozyme markers and 2 coat color genes tentatively ruled out linkage of DMH susceptibility on 7 autosomes. The 47% tumor incidence among 57 male resistant backcross hybrids, regardless of whether their single X chromosome was inherited from the ICR/Ha or C57BL/Ha strain, provides evidence against sex linkage.