Radiosensitivity and effects of repair inhibitors for X-ray-induced chromosomal damage in mouse zygotes in S and G2 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.
Matsuda
Y
Y
Division of Genetics, National Institute of Radiological Sciences, Chiba, Japan.
Tobari
I
I
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects*; D005260:Female; D016195:G2 Phase / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance; D016196:S Phase / Q000528:radiation effects*; D014965:X-Rays; D015053:Zygote / Q000528:radiation effects*
D001549:Benzamides; D003561:Cytarabine; D002110:Caffeine; C025160:3-aminobenzamide