Comparative analysis of caffeine and 3-aminobenzamide as DNA repair inhibitors in Syrian baby hamster kidney cells.
The effects of caffeine and 3-aminobenzamide (3-AB) on Syrian baby hamster kidney cells treated with DNA-alkylating agents and ultraviolet-light suggest that two different DNA-repair mechanisms are involved. Both these agents enhanced the cell kill after methyl methanesulfonate (MMS) treatment. However, enhanced lethality was observed only with caffeine post-treatment when cells were exposed to nitrogen mustard (HN2) or ultraviolet light (UV); 3-AB did not appreciably change cell killing by these agents. With MMS-treated cultures, the effect of caffeine was maximal about 16 h later. The effect of 3-AB on the other hand, was exerted during the first 4 h after exposure to MMS. Caffeine's effect on cell survival could be abolished by low concentrations of cycloheximide, whereas 3-AB's effect could not. Furthermore, the G2 block in cell cycle progression, after MMS treatment, was not observed if the cells were post-treated with caffeine. In the presence of 3-AB, MMS-treated cells were arrested in G2 phase at a much earlier time compared to cells not treated with 3-AB. Finally caffeine post-treatment produced a 10-fold increase in nuclear fragmentation in MMS-treated cells. 3-AB did not cause nuclear fragmentation by itself but further enhanced the nuclear fragmenting effect of caffeine when both agents were present during the posttreatment. Therefore, we propose that 3-AB and caffeine each prevent a different repair mechanism from being effective.
D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D002110:Caffeine / Q000633:toxicity*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects*; D004347:Drug Interactions; D005434:Flow Cytometry; D007399:Interphase / Q000187:drug effects; D007668:Kidney; D007700:Kinetics; D008466:Mechlorethamine / Q000633:toxicity; D008647:Mesocricetus; D008741:Methyl Methanesulfonate / Q000633:toxicity; D014466:Ultraviolet Rays
D001549:Benzamides; D002110:Caffeine; D008466:Mechlorethamine; C025160:3-aminobenzamide; D003513:Cycloheximide; D008741:Methyl Methanesulfonate