Susceptibility to urethan-induced pulmonary adenomas between A/J and C57BL/6J mice: use of AXB and BXA recombinant inbred lines indicating a three-locus genetic model.

For insight into the number of genes governing differential susceptibility such as in mice of the inbred strain A/J (A) highly susceptible to the induction of pulmonary adenomas by urethan in comparison to resistant strain C57BL/6J (B6) mice, tumor induction was studied in the AXB and BXA series of recombinant inbred (RI) strains derived respectively from A female X B6 male and B6 female X A male ancestral lines. Mice from 46 of these lines were given injections with 1 mg urethan/g (body wt), and the tumor number was assessed 4 months later. Lung tumor multiplicity for several RI lines was independently characterized in the Boulder, CO, and Montreal laboratories, and very similar numbers were obtained. Most lines had multiplicities intermediate to those of the progenitor strains, clearly indicating that more than a single gene accounted for the differences in lung tumor susceptibility between A and B6. The tumor incidence and multiplicity data fit very closely to what would be expected under a three-locus model, and we designated these genes "Pas" for pulmonary adenoma susceptibility. One locus called "Pas-1" had an effect on tumor multiplicity greater than that of the other loci.