Tumour Induction in Mouse Epidermal Cells Irradiated by Hot Particles

Abstract

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.

Biokinetics of nuclear fuel compounds and biological effects of nonuniform radiation.

“…Our observations (20,21) suggest that the development of hot-particle-induced skin cancer depends on a few essential cellular and molecular mechanisms. The development of a permanent wound is an essential step in the carcinogenesis induced by nonuniform n-irradiation.…”

“…A femitting hot particle creates a dose gradient around it, causing cell death near the particle. The cells around the lethal zone obtain a sublethal dose, which does not kill the cells but is large enough to cause a random, malignant transformation (17)(18)(19)(20)(21). In Figure 1, a dosimetric model for a hot particle containing 1000 Bq of 106Ru or 14 Ce is shown.…”

“…Most of the theoretical (12,14,15) and experimental studies (see Table 3) have refuted the hot particle hypothesis. However, we have observed that hot particle-induced carcinogenesis is associated with specific biological mechanisms that cannot be explained by mathematical modeling (17)(18)(19)(20)(21). Human Exposure Occupational exposure.…”

“…Lang et al. (20) exposed hairless and nude mice to neutronactivated U02 particles. Within the first two weeks, an ulcer (diameter 1-4 mm) with erythematous and thick edges developed.…”

“…As a consequence of the Chernobyl power plant accident, several theoretical and experimental studies coordinated by the International Atomic Energy Agency were initiated to study possible health hazards associated with the exposure to {3-emitting hot particles (16). Recent experimental studies indicate that conventional dose risk assessment models may underestimate the biological significance of {-emitting hot particles (17)(18)(19)(20)(21).…”