Characterization of the enhancing effect of caffeine on sister-chromatid exchanges induced by ultraviolet radiation in excision-proficient xeroderma pigmentosum lymphoblastoid cells.
Cells of some excision-proficient xeroderma pigmentosum (XP) cell lines are highly sensitive to post-UV caffeine treatment in terms of sister-chromatid exchange (SCE) induction as well as cell lethality. In the present study, we conducted a detailed investigation of the enhancing effect of caffeine on SCE frequency induced by UV in excision-proficient XP cells, and obtained the following results. (1) Continuous post-UV treatment with 1 mM caffeine markedly enhances UV-induced SCEs and such enhanced SCEs occur with similar frequency during either the 1st or the 2nd cell cycle in the presence of caffeine and 5-bromodeoxyuridine (BrdUrd). (2) The high sensitivity of the cells to post-UV caffeine treatment persists for at least 2 days after UV when irradiated cells are held in either the proliferating or the nonproliferating state prior to the addition of BrdUrd. (3) Caffeine exerts its effect on cells in S phase. (4) Neither BrdUrd in the medium nor the incorporated 5-bromodeoxyuridine monophosphate (BrdUMP) in DNA plays an appreciable role in the expression of the enhancing effect of caffeine. The most likely explanation for our findings is as follows. In excision-proficient XP cells, the cause of SCE formation such as UV-induced lesions or resulting perturbations of DNA replication persists until the 2nd round or more of post-UV DNA replication. If caffeine is given as post-UV treatment, such abnormalities may be amplified, resulting in a synergistic increase in SCE frequency.
Tohda
H
H
Department of Pharmacology, Tohoku University, Sendai, Japan.
Oikawa
A
A
D000328:Adult; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D000242:Cyclic AMP / Q000502:physiology; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007399:Interphase / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012854:Sister Chromatid Exchange / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D002110:Caffeine; D000242:Cyclic AMP; D001973:Bromodeoxyuridine