Effects of chemicals on the frequency of sister chromatid exchanges and chromosome aberrations in normal and Bloom's syndrome lymphocytes

Abstract

Bloom's syndrome (BS) lymphocytes, which are characterized by a high incidence of sister chromatid exchangs (SCE, 78.4 per cell), were treated with bifunctional--(MC) and monofunctional--(M--MC) mitomycin C and 4-nitroquinoline-l-oxide (4NQO) either singly or in combination with caffeine, and the effects of the chemicals on the frequency of SCE and chromosome aberrations compared with that in normal lymphocytes. The normal cells were highly sensitive to MC with regard to SCE frequency (10 times over the control level), but not to M--MC and 4NQO, whereas in BS cells, MC, M--MC or 4NQO easily induced SCE up to 'saturation' level, though the relative increase in SCE was not as high (2 times over the control level). The effect of caffeine in combination with these agents was to increase markedly the SCE frequency and that of shattered chromosomes in normal cells, whereas in BS cells the effect of caffeine on SCE was not synergistic with these agents, i.e. the SCE level achieved was not significantly increased over that obtained by the simple addition of these agents. The frequency of mitotic chiasmata was significantly increased by MC in BS cells; however, no significant difference was found in the distribution of chiasmata among chromosome regions between treated and untreated materials. This differs from the reported action of MC on cultured lymphocytes of normal subjects, where chiasmata are concentrated at secondary constrictions and centromeres of chromosomes nos. 1, 9 and 16. Possible differences in the mechanisms inducing SCE and chromosome aberrations in chemically-treated normal and Bloom's syndrome cells are discussed.