Host genes affecting survival period of chemically induced bladder cancer in mice

Treatment of C57BL/6 J (B6) and NON male mice with N-butyl-N-(4-hydroxybuty l)nitrosamine (BBN) resulted in a high incidence of bladder cancer. The mea n survival period, however, differed significantly by strain: 481 +/- 219 d ays in B6 (n = 31) and 203 +/- 119 days in NON (n = 30) (P < 0.0001). Major causes of death were renal failure due to obstruction of the urinary tract , or local invasion of tumors. The fact that the BBN-treated NON x B6 recip rocal F1 mice had survival periods as short as those of the parental NON mi ce suggests a genetically dominant susceptibility in NON or recessive resis tance in B6. A linkage analysis of 248 back-cross mice to B6 suggested at l east two quantitative trait loci determining the length of the survival per iod: one was mapped close to D2Mit260 (logarithm of odds, LOD, score 2.21), a microsatellite marker locus 83 cM from the centromere on chromosome 2, a nd another was close to D6Mit159, 7 cM from the centromere on chromosome 6 (LOD score 2.51).