Bystander effect for chromosomal aberrations induced in wild-type and repair deficient CHO cells by low fluences of alpha particles

Abstract

We have previously shown that when confluent cultures of mammalian cells are exposed to very low fluences of alpha particles, fluences whereby as few as 1% of the cell nuclei are traversed by a single particle, genetic effects including specific gene mutations and sister chromatid exchanges (SCE) are induced in neighboring, non-irradiated "bystander" cells. The present investigation was designed to examine the induction of chromosomal aberrations in wild-type CHO cells and its DNA double strand break repair deficient mutant xrs-5 by a broad range of alpha particle fluences yielding mean doses of 0.17-200cGy. The dose-response curve for the induction of aberrations was curvilinear for both cell lines, with a greater effect occurring at very low fluences owing to aberrations arising in bystander cells. These aberrations were predominantly of the chromatid-type. With such fluences, the number of cells with induced aberrations per nucleus irradiated increased up to 4-fold in CHO cells and 15-fold in xrs-5 cells over that expected if aberrations occurred only in irradiated cells. These results are discussed in terms of the hypothesis that the primary DNA damage in bystander CHO cells is oxidative base damage leading to a relatively small bystander effect for gross chromosomal aberrations as compared with mutations or SCE; the larger bystander effect in xrs-5 cells is the result of oxidative damage and non-repaired DNA strand breaks which may result from opposed oxidative lesions.