Radon-induced cancer: a cell-based model of tumorigenesis due to protracted exposures.
In 1982, results with C3H mouse embryo cells showed that the frequency of neoplastic transformation was enhanced when exposures to fission-spectrum neutrons were protracted in time. This finding was unexpected because the opposite was found with low-LET radiations. Similar neutron enhancements were reported with normal life-span Syrian hamster embryo cells, and with human hybrid cells. Because other studies did not confirm the preceding, in 1990--at a conference convened by the US Armed Forces Radiobiological Research Institute--a biophysical model was proposed to explain the basis for the enhancement observed in some experiments but not in others. The model attributed special sensitivities, related to killing and neoplastic transformation, to cells in and around mitosis. Subsequently, it was shown that late G2/M phase cells constituted this window of sensitivity. In the instance of tumorigenesis, the model predicted that protracted exposures to a high-LET radiation would result in enhanced frequencies of transformation providing that susceptible cells were cycling or could be induced to cycle. The model explained data on lung tumour induction in rats breathing radon at different concentrations, and uranium miners working in atmospheres containing different concentrations of radon. The model also explains the anomalous finding that lung cancer deaths are often sublinearly correlated with indoor radon concentration.
Elkind
M M
MM
Department of Radiological Health Sciences, Colorado State University, Fort Collins 80523.
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004781:Environmental Exposure; D016195:G2 Phase / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D011886:Radon / Q000009:adverse effects*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D013755:Tetradecanoylphorbol Acetate; D011886:Radon