Defective DNA repair and increased lethality in ataxia telangiectasia cells exposed to 4-nitroquinoline-1-oxide.

Ataxia telangiectasia (AT) is a rare autosomal recessive disorder in man characterized by progressive loss of muscular coordination (due to neurodegeneration) and permanent dilation of the small blood vessels of the eyes and skin. AT patients also have repeated sinopulmonary infections, immune defects associated with thymus underdevelopment, and abnormal endocrine functions. Affected patients are at high risk of developing malignancy, particularly lymphomas and lymphatic leukaemias, and there are clinical indications that AT patients are hypersensitive to conventional radiotherapy administered for treatment of malignancy. Cultured diploid fibroblasts from AT donors are consistently hypersensitive to ionizing radiation, apparently due to defective enzymatic repair of radiogenic DNA damage. We have determined the survival responses and DNA repair abilities of AT cells exposed to 4-nitroquinoline-1-oxide (4NQO), a chemical carcinogen whose DNA-damaging properties partially mimic those of ionizing radiation. We report here that certain AT cell strains show hypersensitivity to inactivation by 4NQO and defective repair of 4NQO-induced adducts in DNA.