LOCALIZATION OF A NOVEL CHROMOSOME-7 LOCUS THAT SUPPRESSES DEVELOPMENT OF N-METHYL-N-NITROSOUREA - INDUCED MURINE THYMIC LYMPHOMAS

N-Methyl-N-nitrosourea (MNU) is a potent carcinogen that causes the de velopment of murine thymic lymphomas. MNU-induced tumor incidence vari es considerably among different inbred mouse strains. In particular, t he AKR strain is highly susceptible, whereas the C57L strain is highly resistant to MNU-induced lymphoma formation. Crosses between AKR and C57L mice were established to investigate the genetic basis for the di fferential susceptibility of these inbred strains. A strong associatio n between MNU-induced lymphoma development and coat color was observed in (AKR x C57)F2 and AKR x (AKR x C57)F1 progeny such that albino mic e developed a higher tumor incidence than nonalbino animals. These dat a suggest that a locus on chromosome 7 influences tumor development. A nalysis of four additional polymorphic loci (D7RpZ Fes, Hbb, and Int-2 ) on chromosome 7 in AKR x (AKR x C57)F1 backcross mice revealed a sig nificant linkage between high tumor incidence and homozygous inheritan ce of AKR alleles at the albino (tyrosinase) and Hbb loci. Thus, inher itance of at least one C57L allele at the albino or Hbb loci was assoc iated with protection against MNU-induced lymphoma development. There was no association between tumor incidence and genotype at the D7RpZ F es, or Int-2 loci. Taken together, the data suggest that whereas C57L mice contain a dominant tumor suppressor gene on chromosome 7, in the AKR strain both alleles at this locus are defective resulting in enhan ced susceptibility to MNU-induced lymphomagenesis.