The genetic basis of susceptibility to leukemia induction in mice by 3-methylcholanthrene applied percutaneously.
Susceptibility to leukemia induction in mice by skin painting with 3-methylcholanthrene (MCA) is strain-specific, occurring only in strains relatively resistant to MCA-induced skin tumors. The Ah locus, which has a dominant allele (Ahb) for inducibility of the aryl hydrocarbon hydroxylase (AHH) enzyme system and a recessive allele (Ahd) for noninducibility, appears to be the major determinant of this trait. MCA-painted mice of strains and crosses carrying the Ahb allele usually show a high incidence of skin tumors (papillomas which may evolve into malignant tumors) and little or no leukemia, whereas in mice homozygous for the Ahd allele the treatment usually induces a high incidence of leukemia and few or no skin tumors. Among mice of a segregating backcross generation including both Ahb/Ahd heterozygotes and Ahd homozygotes, the occurrence of skin tumors was correlated directly with AHH inducibility and inversely with the leukemic response. Mice of Ahb strains with a high level of endogenous murine leukemia (MuLV) expression (C58, PL) show a much weaker skin tumor response than expected but no increase in leukemia incidence, and this observation tends to confirm the previous finding that MuLV infection of mice of low-MuLV strains results in reduced susceptibility to MCA tumorigenesis.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction; D006720:Homozygote; D007942:Leukemia, Experimental / Q000139:chemically induced / Q000235:genetics*; D008748:Methylcholanthrene / Q000008:administration & dosage; D051379:Mice; D010212:Papilloma / Q000139:chemically induced; D012878:Skin Neoplasms / Q000139:chemically induced
D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases