Allelic imbalance in mammary carcinomas induced by either 7,12-dimethylbenz[a]anthracene or ionizing radiation in rats carrying genes conferring differential susceptibilities to mammary carcinogenesis.

To identify and compare the genetic lesions associated with tumorigenesis in rats carrying the mammary carcinoma suppressor (MCS) 1 gene, we induced mammary carcinomas in (Wistar Furth (WF) x Copenhagen (Cop))F1 rats by using either 7,12-dimethylbenz[a]anthracene (DMBA) or radiation. The tumors were screened for allelic imbalances by using polymerase chain reaction and 65 polymorphic microsatellite markers spanning the genome. No allelic imbalance was detected at the mapped location of MCS-1 on chromosome 2; however, a scan of the genome revealed random allelic imbalances in the radiation-induced tumors. In addition, non-random loss of heterozygosity (LOH) on chromosome 1 in the DMBA-induced tumors was documented. We then screened three other subsets of DMBA- and radiation-induced mammary carcinomas from (WF x Fischer (F344))F1, (Wistar Kyoto x F344)F1, and (F344 x Cop)F1 rats for imbalance on chromosomes 1 and 2. No allelic imbalance was detected in the MCS-1 region of chromosome 2 in any of the tumors screened. Nonrandom imbalance on chromosome 1 was detected but only in the DMBA-induced tumors from the (F344 x Cop)F1 rats. Thus, only Cop-derived F1 rats have mammary tumors with the chromosome 1 imbalance; however, the imbalance does not favor the Cop parental allele. We also analyzed the DMBA-induced tumors with LOH at chromosome 1 for Ha-ras codon 61 mutation and found no association. These results suggest that loss of the MCS-1 Cop allele is not required for tumor formation, that the genetic background of the F1 rat appears to influence the type of genetic lesion identified in the mammary tumors, and that there is no association between Ha-ras codon 61 mutation and chromosome 1 imbalance in our model system.