Potentially Lethal Damage

IntroductionThere is much evidence to support the hypothesis that DNA, and/or structures containing DNA, are the sensitive sites in mammalian cell killing by ionizing radiation (for a review see Elkind 1977) .Similarly, lethality which results from the exposure of mammalian cells to far-ultra-violet (far-U .V .)light (mainly 254nm radiation) is attributed to DNA photolesions, an association based .partly on the extensive findings with bacterial mutants implicating DNA damage in far-U .V .killing (see, for example, Setlow and Setlow, 1972), on the deficient repair of DNA in xeroderma pigmentosum cells (Bootsma, Mulder, Pot and Cohen 1970, Cleaver, 1970, 1974, Setlow, Regan, German and Carrier 1969, Robbins, Kraemer, Lutzner, Festoff and Coon 1974) and on the similarity of DNA photolesions in bacteria and mammalian cells .However, perhaps the clearest basis for a cause-effect relationship between DNA damage and lethality in repair-competent cells is the exposure of mammalian cells to non-ionizing radiation after they have incorporated 5-bromodeoxyuridine (BUdR) into their DNA (see, for example, Ben-Hur and Elkind 1972 a, b) .In this case, DNA damage vis-k-vis cell killing is a consequence of the chemical events that follow the photodebromination of bromouracil in DNA (see, for example, Hutchinson 1973) .In spite of the foregoing indications that the genome is involved in cell killing by both ionizing and non-ionizing radiations, the biological effects of these two radiations are frequently quantitatively and, in some cases, qualitatively different .Differences exist with respect to the inhibition of DNA synthesis (see, for example, Cleaver 1967, Whitmore, Stanners, Till and Gulyas 1961, Elkind, Moses and Sutton-Gilbert 1967 a), the extent of pre-replicational, single-strand DNA repair (Regan, Setlow and Ley 1971, Lehmann 1972, Painter and Young 1972), the lengths of induced division delay for a given killing effect (Humphrey, Dewey and Cork 1963, Bootsma and Humphrey 1968, Han, Sinclair and Yu 1971, Elkind, Han and Volz 1963), the age-response patterns (Sinclair and Morton 1965, Rauth and Whitmore 1966, Han and Sinclair 1969) and the rates of sublethal damage repair (Domon and Rauth 1973, Todd 1973, Elkind, Sutton-Gilbert, Moses and Kamper 1967 b).In this report we describe differences in the expression of potentially lethal damage as a further indication of qualitative differences in the lethal lesions due to ionizing and non-ionizing radiation .1978 U .S .Government .