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 tumorigene sis in rats carrying the mammary carcinoma suppressor (MCS) 1 gene, we induced mammary carcinomas in (Wistar Furth (WF) x Copenhagen (Cop))F -1 rats by using either 7,1 2-dimethylbenz[a]anthracene (DMBA) or radi ation. The tumors were screened for allelic imbalances by using polyme rase 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 rando m allelic imbalances in the radiation-induced tumors. In addition, non random loss of heterozygosity (LOH) on chromosome 1 in the DMBA-induce d tumors was documented. We then screened three other subsets of DMBA- and radiation-induced mammary carcinomas from (WF x Fischer (F344))F- 1, (Wistar KyotoxF344)F-1, and (F344xCop)F-1 rats for imbalance on chr omosomes 1 and 2. No allelic imbalance was detected in the MCS-1 regio n of chromosome 2 in any of the tumors screened. Nonrandom imbalance o n chromosome 1 was detected but only in the DMBA-induced tumors from t he (F344xCop)F-1 rats. Thus, only Cop-derived F-1 rats have mammary tu mors with the chromosome 1 imbalance; however, the imbalance does not favor the Cop parental allele. We also analyzed the DMBA-induced tumor s with LOH at chromosome 1 for Ha-ras codon 61 mutation and found no a ssociation. These results suggest that loss of the MCS-1 Cop allele is not required for tumor formation, that the genetic background of the F-1 rat appears to influence the type of genetic lesion identified in the mammary tumors, and that there is no association between Ha-ras co don 61 mutation and chromosome 1 imbalance in our model system. (C) 19 96 Wiley-Liss, Inc.