Radon Mutagenic Effect

Induction of a Bystander Mutagenic Effect of Alpha Particles in Mammalian Cells

Center for Radiological Research, College of Physicians and Surgeons and Environmental Health Sciences, School of Public Health, Columbia University October 1, 1999

Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected AL cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 mM dose of lindane, which inhibits cell– cell communication, significantly de-creased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic.

We further examined the mutagenic yield when 5–10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no by-stander effects.

Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell to cell communication process play a critical role in mediating the by-stander phenomenon.