The Induction of Thymine Dimers in Ultraviolet-Irradiated Mammalian Cells

Abstract

It is well established that both gene mutations and chromosome aberrations can be induced by ultraviolet (UV) light (see review: 1). The action spectrum for mutation implicates nucleic acid absorption (2), and the action spectrum for the UVinduced chromosome aberrations in Tradescantia pollen grains approximately parallels the absorption spectrum of nucleic acids (3). Similarly, the frequency of UVinduced chromosome aberrations in mammalian cells varies with wavelength and reaches a peak around 2650 A (4). It has been further demonstrated that substitution of thymidine by 5-bromodeoxyuridine or 5-iododeoxyuridine greatly enhances the UV-sensitivity in the induction of mammalian chromosome breaks. These results suggest that DNA is the primary target of the UV injury that leads to chromosome aberrations (4). The effects of UV on nucleic acids and their constituents have been the subject of numerous investigations (see reviews: 5, 6). The kinds of UV damage to DNA include photohydration, cross-linkage, and the formation of thymine dimer. In particular, recent work has indicated that thymine dimerization may account for a large proportion of the UV-induced damage to transforming activity (7) and probably for much of the loss of DNA synthetic capacity in bacteria (8, 9). It has been found that the photoreactivation of transforming principle can be accounted for by dimer splitting (7). Furthermore, in certain strains of Escherichia coli, UV-induced thymine dimers, together with a few neighboring nucleotides, can be excised by what seems to be a dark repair process (10, 11). If the conclusion is correct that chromosomal DNA is the site of UV injury that leads to chromosome breaks, it is of interest to determine the nature of the induced molecular alteration(s) responsible for chromosome breaks. This report presents