Tumour induction in mouse epidermal cells irradiated by hot particles

We have shown elsewhere that highly non-uniform exposure to ionizing radiation from authentic Chernobyl-released and artificially-produced hot particles (fragments of nuclear fuel) transform fibroblastic 10T1/2 cells in vitro effectively. We have also shown that hot-particle exposure leads to mutation and overexpression of the tumour suppressor gene p53 (and some other growth-related genes) in mouse skin in vivo at a high frequency. In the present paper it is shown that hot-particles produced by irradiating natural uranium with slow neutrons, when implanted (immobilized) under the skin of hairless and nude mice, induce epidermal tumours in excess compared with the conventional non-threshold stochastic model of radiation-induced cancer. One explanation for the effectiveness of the hot-particle exposure, under the present assay conditions, is that the same cells in which specific radiation-induced DNA damage is most likely to occur, are forced into sustained mitotic activity in the chronic wound which develops around the radiation source (combined genotoxic and nongenotoxic effects). The results are consistent with a role for cell proliferation in multistage carcinogenesis in mouse skin.