Induction of chromosome shattering and micronuclei by ultraviolet light and caffeine. I. Temporal relationship and antagonistic effects of the four deoxyribonucleosides.

Abstract

It is known that nucleosides may have antimutagenic and anticlastogenic effects. Here, we have investigated the influence of nucleosides on the induction of shattered chromosomes (fragmentation and/or pulverization of chromosomes of a mitotic cell) and of micronuclei by ultraviolet (UV) light and caffeine. Asynchronous cell cultures of a V79 subline of the Chinese hamster were irradiated at wavelength 254 nm using fluences up to 5.2 joules/m2. Following irradiation, the cells were postincubated either with 1.0 mM or 2.0 mM caffeine alone or with caffeine plus the four deoxyribonucleosides (dXs) (concentration 0.1 mM each). After different incubation times (three to 24 hours), chromosome preparations were performed. In other experiments, synchronized cells were used. The percentage of metaphase spreads with shattered chromosomes and the percentage of cells with micronuclei were determined. Post-treatment with caffeine alone resulted in shattered chromosomes in a high percentage of cells at the first post-irradiation mitosis as described previously. Formation of cells with micronuclei was observed only afer the appearance of mitotic cells with shattered chromosomes, the maximum percentage of cells with micronuclei being smaller than the maximum percentage of cells with shattered chromosomes. The strong potentiating effect of UV-light plus caffeine was significantly reduced, however, if the post-treatment was performed with caffeine plus nucleosides. A significant reduction was also observed in the percentage of micronuclei. An evaluation of the mitotic indices and of cell-cycle parameters indicates that the effect of nucleosides was not due to enhanced interphase death.