Abstract
The health effects of low-dose radiation should be evaluated in combination with chemicals as humans are continuously exposed to a variety of chemical agents. Carcinogenesis is one of the most important concerns regarding to the possible effects from low-dose radiation. Of various environmental hazardous compounds, the most prominent factor associated with the increase in cancer risk is cigarette smoke. Although cigarette smoke contains more than 40 human carcinogens, the most carcinogenic nitrosamino compound is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the present study, the effects of low dose-rate irradiation on the genotoxicity of NNK were examined. The female gpt delta mice (7 weeks of age) were either treated with gamma-irradiation at low dose rates (0, 0.5, 1.0 or 1.5 mGy/h x 22 h/day) for 31 days or combined with NNK (2 mg/mouse/day, i.p.) administration for 4 continuous days in the middle course of irradiation. The gpt and Spi- mutations in the lung and liver of the mice were analyzed. NNK treatments enhanced the gpt mutation frequencies (MFs) 3-8 times and 12-19 times in the lung and in the liver, respectively. However, no modulating effects of low dose-rate radiation were observed in both organs. In the Spi- MFs, large deletions with the size of more than 1 kb increased in the irradiated groups compared to those in the unirradiated groups. Analyses of the effects of low dose-rate irradiation on NNK-induced deletion mutations are in progress.
