INHALED RADON-INDUCED GENOTOXICITY IN WISTAR RAT, SYRIAN-HAMSTER, ANDCHINESE-HAMSTER DEEP-LUNG FIBROBLASTS IN-VIVO

This study was performed (1) to provide a comparison of the genotoxic effects of inhaled radon and radon progeny, referred to as radon in th is paper, among three species of rodents: Wistar rats, Syrian hamsters , and Chinese hamsters; (2) to determine if initial chromosome damage was related to the risk of induction of lung cancer; and (3) to evalua te the tissue repair and long-term presence of cytogenetic damage in r espiratory tract cells. These species were selected because Syrian ham sters are very resistant to radon induction of lung cancer and Wistar rats are sensitive; no literature is available on the in vivo effects of radon in the Chinese hamster. Exposure-response relationships were established for the rats and Syrian hamsters while the Chinese hamster s received a single exposure of radon. At 4 h (0.2 days), 15 days, and 30 days after the highest WLM exposure to radon, Wistar rats, Chinese hamsters, and Syrian hamsters were killed, and lung fibroblasts were isolated and grown in culture to determine the frequency of induced mi cronuclei. Animals at each level of exposure showed an increase in the frequency of micronuclei relative to that in controls (P < 0.05). The exposure-response relationship data for rats and Syrian hamsters kill ed 0.2 days after the end of exposure were fit to linear equations (mi cronuclei/1000 binucleated cells = 15.5 +/- 14.4 + 0.53 +/- 0.06 WLM a nd 38.3 +/- 15.1 + 0.80 +/- 0.08 WLM, respectively). For the single ex posure level used (496 WLM) in Chinese hamsters killed at 0.2 days aft er exposure, the frequency of micronuclei/1000 binucleated cells/WLM w as 1.83 +/- 0.02. A comparison of the sensitivity for induction of mic ronuclei/WLM illustrated that Chinese hamsters were three times more s ensitive than rats. The Syrian hamsters also showed a significantly el evated response (P < 0.05) relative to rats. These data suggest that i nitial chromosome damage is not the major factor responsible for the h igh rate of radon-induced cancer in rats relative to Syrian hamsters. The frequency of micronuclei in radon-exposed rats, Syrian hamsters, a nd Chinese hamsters significantly decreased (P < 0.05) as a function o f time after the exposure. The rate of loss of damaged cells from the lung was greatest in the Chinese hamsters, followed by Wistar rats and Syrian hamsters, respectively. Our experiments demonstrated that the mammalian lung fibroblast/micronucleus method has the potential to (1) detect species differences in the induction of in vivo genotoxic dama ge in the lungs by inhaled environmental agents; (2) evaluate exposure -response relationships for in vivo induction of genetic damage; and ( 3) determine the persistence in vivo of preclastogenic and premutageni c lesions in cell populations.