The bystander effect in radiation oncogenesis: I. Transformation in C3H 10T(1)/(2) cells in vitro can be initiated in the unirradiated neighbors of irradiated cells

It has long been accepted that radiation-induced genetic effects require th at DNA be hit and damaged directly by the radiation. Recently, evidence hai accumulated that in cell populations exposed to low doses of or particles, biological effects occur in a larger proportion of cells than are estimate d to have been traversed by at particles. The end points observed include c hromosome aberrations, mutations and gene expression. The development of a fast single-cell microbeam now makes it possible to expose a precisely know n proportion of cells in a population to exactly defined numbers of a parti cles, and to assay for oncogenic transformation. The single-cell microbeam delivered no, one, two, four or eight a particles through the nuclei of all or just 10% of C3H 10T1/2 cells. We show that (a) more cells can be inacti vated than were actually traversed by ex particles and (b) when 10% of the cells on a dish are exposed to or particles, the resulting frequency of ind uced transformation is not less than that observed when every cell on the d ish Is exposed to the same number of or particles. These observations const itute evidence suggesting a bystander effect, i.e,, that unirradiated cells are responding to damage induced in Irradiated cells, This bystander effec t in a biological system of relevance to carcinogenesis could have signific ant implications for risk estimation for low-dose radiation. (C) 2001 by Ra diation Research Society.