Loss-of-heterozygosity analysis of 6-thioguanine-resistant mutants induced by radon exposure in mouse FM3A cells.

Radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas such as buildings and underground mines. The ubiquitous occurrence of radon in the environment is the primary cause of harmful radiation exposure to the public. To investigate the mutagenic effect of radon, mouse FM3A cells growing on soft agarose plates were exposed to alpha particles disintegrated from radon-222 and daughter elements. Mutation induction at the hypoxanthine phosphoribosyl transferase (Hprt) allele was examined at radon concentrations of 10, 230, 1,100, 6,500, 200,000, 1,000,000, and 10,000,000 Bq/m(3) for an exposure period of 1 week. A typical inverse dose-rate effect was observed in the frequencies of 6-thioguanine-resistant (6TG(R)) mutations, and lower mutation frequencies were exhibited at 230, 1,100, 6,500, and 200,000 Bq/m(3) than at 10, 1,000,000, and 10,000,000 Bq/m(3). Loss-of-heterozygosity (LOH) analysis at the Hprt locus revealed that deletion mutations were dominant at radon concentrations of 230, 1,100, 6,500, and 10,000,000 Bq/m(3), but not at 10, 200,000, and 1,000,000 Bq/m(3). These results suggested that alpha particles released from radon in the normal atmosphere did not exhibit the measured mutagenic effect in mouse FM3A cells, but that increased concentrations of radon led to a significant increase in the mutagenic effect of radon. At 6,500 Bq/m(3), radon exposure induced the least number of 6TG(R) mutants but all had LOH deletion mutations, which is the typically observed type of mutation in radiation carcinogenesis. Our results suggest that certain concentrations of environmental radon may have specific carcinogenic potential, and it should be avoided by proper ventilation wherever possible.