Genetics of colon carcinogenesis in mice treated with 1,2-dimethylhydrazine.
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 two inbred mouse strains, the 100% susceptible ICR/Ha and completely resistant C57BL/Ha. Mice, 12 to 14 weeks old, received 22 successive weekly s.c. injections of 0.35% aqueous solution of DMH buffered to pH 6.5. A dose of 15 mg/kg/mouse/week produced invasive colon adenocarcinomas in all ICR/Ha males and females (60 of 60) within 22 weeks. None of the 90 C57BL/Ha mice developed DMH tumors during 44 weeks of observation. Susceptibility to the carcinogen was dominant, as indicated by 100% colon tumor incidence in reciprocal ICR/Ha X C57BL/HaF1 hybrids (68 of 68) and in the susceptible backcross ICR/Ha X F1 (42 of 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. Likewise, tumor yield in resistant backcross mice of genotype C57BL/Ha X F1 (46 of 117) is not out of line with the anticipated 1:1 ratio in the latter type of test hybrids. Tests with five isozyme markers and two coat color genes have tentatively ruled out linkage of DMH susceptibility on seven 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.
D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics*; D003433:Crosses, Genetic; D004127:Dimethylhydrazines; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006834:Hydrazines; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics; D013045:Species Specificity
D004127:Dimethylhydrazines; D006834:Hydrazines