Abstract
The loss of heterozygosity (LOH) analysis of cancer genome is a powerful method to identify tumor suppressor genes. We have reported that LOH of the Ikaros locus, which encodes a key transcription factor for lymphoid cell differentiation, is frequently observed in radiation-induced mouse thymic lymphoma, as an example of radiation-specific alteration of a tumor suppressor gene. On the other hand, epidemiologic studies of atomic bomb survivors indicate that the mammary gland is the most susceptible organ to solid tumor induction by radiation. Most studies have failed to identify clear genetic alterations in radiation-induced mammary cancer. This prompted us to search for characteristic LOH loci in radiation-induced rat mammary cancers. [Methods] Female Sprague-Dawley (SD) rats at 7 weeks of age were exposed to either gamma-rays (0, 0.5, 1 and 2 Gy), a chemical carcinogen PhIP (40 mg/kg/day, 10 days), or a combination thereof. Genomic DNA was extracted from collected mammary cancers and ear skins of corresponding individuals. Sizes of PCR products were compared between cancers and ear skins for loci that are reported to show PhIP-specific LOH. Hybrid (F1) rats between susceptible SD and resistant Copenhagen rats were generated and irradiated with 4 Gy of gamma-rays for a more systematic LOH analysis. [Result] Relatively high frequency of LOH was observed in PhIP-induced cancers (6 of 28, 21%) compared with gamma-ray-induced and combination-induced cancers (6 and 0%, respectively). Mammary cancer developed in 18 of 29 (62%) F1 rats. The LOH analysis of these cancers is currently underway and will be reported.
