Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells

Subpopulations that are genetically predisposed to radiation-induced cancer could have significant public health consequences. Individuals homozygous for null mutations at the ataxia telangiectasia gene are indeed highly radi osensitive, but their numbers are very small. Ataxia Telangiectasia heteroz ygotes (1-2% of the population) have been associated with somewhat increase d radiosensitivity for some end points, but none directly related to carcin ogenesis. Here, intralitter comparisons between wild-type mouse embryo fibr oblasts and mouse embryo fibroblasts carrying ataxia telangiectasia mutated (ATM) null mutation indicate that the heterozygous cells are more sensitiv e to radiation oncogenesis than their normal, litter-matched, counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally-significant radiosensitive human subpopulatio n.