Radiosensitivity and Effects of Repair Inhibitors for X-ray-induced Chromosomal Damage in Mouse Zygotes in S and G 2 Phases

The potentiation effects of arabinofuranosyl cytosine (ara-C), hydroxyurea, 3-aminobenzamide, and caffeine on the yield of chromosome aberrations were examined at the first-cleavage metaphase in mouse zygotes irradiated with X-rays in S and G2 phases (7.5 and 12 h after insemination respectively) in vitro. Potentiation effects were found in both S and G2 for all chemicals except ara-C. Caffeine completely released G2 arrest, which was not overcome by any other chemicals, and enhanced chromosome aberrations most effectively. Caffeine enhanced chromosome aberrations more in G2 irradiation than in S irradiation, and the frequency of chromatid-type aberrations was remarkably enhanced in G2 irradiation. The results in this study demonstrated an existence of two types of caffeine effects in the mouse zygotes irradiated in S and G2; a cancellation of G2 arrest and direct inhibition of DNA repair pathways. The chromosomal damage induced in G2 was effectively repaired by a repair pathway, which is affected by caffeine, on the other hand, the progression of cell cycle, not repair inhibition, was a major factor of caffeine effect on the yield of chromosome aberrations in S irradiation.