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 radiosensitive, but their numbers are very small. Ataxia Telangiectasia heterozygotes (1-2% of the population) have been associated with somewhat increased radiosensitivity for some end points, but none directly related to carcinogenesis. Here, intralitter comparisons between wild-type mouse embryo fibroblasts and mouse embryo fibroblasts carrying ataxia telangiectasia mutated (ATM) null mutation indicate that the heterozygous cells are more sensitive 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 subpopulation.
Smilenov
L B
LB
Center for Radiological Research, Columbia University, 630 West 168th Street, New York, NY 10032, USA. lbs5@columbia.edu
Brenner
D J
DJ
Hall
E J
EJ
D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000528:radiation effects*; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D011836:Radiation Tolerance / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases