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.

UV micro-irradiation of the Chinese hamster cell nucleus and caffeine post-treatment immunocytochemical localization of DNA photolesions in cells with partial and generalized chromosome shattering

“…This effect has recently been elucidated in more detail by C. who found that GCS was induced by whole-cell irradiation of Chinese hamster cells at the first post-irradiation mitosis when the UV fluence exceeded a 'threshold' value in the sensitive phases of the cell cycle (G1 and S). These results and the finding of antagonistic effects of deoxyribonucleosides (C. Cremer et al, 1980a) are consistent with the view that DNA photolesions play a major role in the induction of GCS.…”

Induction of chromosome shattering by ultraviolet light and caffeine: The influence of different distributions of photolesions

“…Cells of a V79 Chinese hamster subline were grown as described (C. Cremer et al, 1980a. In these cells, caffeine potentiates the chromosome-damaging effects of ultraviolet light (C. Cremer et al, 1980a.…”

“…In these cells, caffeine potentiates the chromosome-damaging effects of ultraviolet light (C. Cremer et al, 1980a.…”

“…Mitotic cells were scored for chromosomal 35 damage and classified according to the following criteria (T. Cremer et al, 1980;C. Cremer et al, 1980a: Class A: no chromosomal alterations visible; Class B: single defects (one, occasionally two aberrations); Class C: more than two aberrations are found but the majority of chromosomes remains intact; Class D: aberrant morphology in the majority of chromosomes, only one or several chromosomes remaining intact; Class E: all chromosomes are affected (fragmentation and/or pulverization): generalized chromosome shattering (GCS).…”

“…A striking phenomenon, which is observed after whole cell irradiation with UV light (?~--254 nm) and caffeine posttreatment, is the frequent occurrence of cells with generalized chromosome shattering (GCS; fragmentation and/or pulverization of all chromosomes of a mitotic cell; Nilsson and Lehmann, 1975;C. Cremer et al, 1980a.…”