Chemical mutagen hypersensitivity in ataxia telangiectasia

Abstract

THE growth of knowledge about DNA replication and repair in bacteria has been aided by the availability of a series of mutations specifically affecting these processes. Almost invariably, defects in repair processes result in an alteration in the sensitivity of cells to ionising radiation and other mutagenic agents. Knowledge is much less advanced for animal cells, although information has been obtained using cells from patients with, for example, xeroderma pigmentosum which have provided six possible mutants in DNA repair^1,2. The diseases classified as chromosome breakage syndromes—ataxia telangiectasia (AT), Fanconi's anaemia and Bloom's syndrome—may also provide a rich source of DNA metabolic mutants. The frequent association of defective DNA metabolism with mutagen sensitivity has suggested an approach to the study of chromosome breakage syndromes. Finkelberg et al.³ have found that Fanconi's anaemia cells are abnormally sensitive to mitomycin C (MC). We have now used this approach to determine whether cells from AT patients are potentially defective in DNA metabolism. We examined their sensitivity to actinomycin D, MC and methyl methane sulphonate (MMS), and the results indicate that AT cells are clearly more sensitive to actinomycin D and that responses to MMS and MC are more variable.