Genetic, cytogenetic, and carcinogenic effects of radon: A review

Abstract

Radon exposure has been linked to lung carcinogenesis in both human and animal studies. Studies of smoking and nonsmoking uranium miners indicate that radon alone is a risk factor for lung cancer at the levels encountered by these miners, although the possibility exists that other substances in the mine environment affect the radon-induced response. The relevance of data from mines to the lower-exposure home environment is often questioned; still, a recent study of miners exposed to relatively low radon concentrations demonstrated a statistically significant increase for lung and laryngeal cancer deaths. In two major series of experiments with rats, the primary carcinogenic effect found was respiratory tract tumors, and evidence for an inverse exposure-rate effect was also noted. Although this inverse dose-rate effect also has been described in underground miner studies, it may not similarly apply to radon in the home environment. This observation is due to the fact that, below a certain exposure, cells are hit once or not at all, and one would not expect any dose-rate effect, either normal or inverse. Because some chromosome aberrations persist in cycling cells as stable events, cytogenetic studies with radon are being performed to help complete the understanding of the events leading to radon-induced neoplasia. Radon has been found to induce 13 times as much cytogenetic damage (as measured by the occurrence of micronuclei) than a similar dose of 60Co. A wide variety of mutation systems have demonstrated alpha-particle mutagenesis; recent investigations have focused on the molecular basis of alpha-induced mutagenesis. Gene mutations are induced by radon in a linear and dose-dependent fashion, and with a high biological effect relative to low-LET irradiation. Studies of the hprt locus show that approximately half of the alpha-induced mutations arise by complete deletion of the gene; the remaining mutations are split between partial deletions, rearrangements, and events not detectable by Southern blot or PCR exon analysis. Although other mutation systems do not show the same spectra as observed in the hprt gene (suggesting that the gene environment affects response), DNA deletions or multilocus lesions of various size appear to be predominant after radon exposure. As data emerge regarding radon-induced changes at the chromosomal and molecular level, the mechanisms involved in radon carcinogenesis are being clarified. This information should increase the understanding of risk at the low exposure levels typically found in the home.