Enhanced synergism between caffeine and mitomycin C in the induction of cytogenetic aberrations in thymidine kinase-deficient Friend murine erythroleukaemia cells.
The thymidine kinase-deficient subclone, 707BUF, of the Friend murine leukaemia cell line exhibits increased sensitivity to the induction of cytogenetic aberrations by mitomycin C (MMC) relative to wild-type clone 707. It has been suggested that thymidine kinase-deficient cells may be highly mutagen-sensitive through an imbalance of nucleotide pools rendering excision repair error-prone. In this study clone 707 Friend leukaemia cells were compared with subclone 707BUF for sensitivity to the potentiating effect of caffeine on MMC-induced cytogenetic aberrations. The results indicate that although potentiation of mitomycin C-induced cytogenetic damage occurs in both clone 707 and in subclone 707BUF following caffeine treatment, the mutagen-sensitive thymidine kinase-deficient subclone 707BUF had enhanced potentiation by caffeine of MMC-induced cytogenetic damage relative to wild-type clone 707. It is suggested that caffeine may enhance mutagen sensitivity by inhibiting post-replication repair processes and may perhaps also indirectly reduce the effectiveness of the excision repair system by inhibiting the mutagen-induced G2-delay. Clone 707 wild-type cells in the presence of caffeine could then continue to repair DNA damage through an intact though less effective excision repair system, whilst the thymidine kinase-deficient subclone 707BUF would, in the presence of caffeine, be rendered highly mutagen sensitive, being only able to repair DNA damage through an error-prone excision repair process.
D000818:Animals; D002110:Caffeine / Q000009:adverse effects*; D002460:Cell Line; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D007942:Leukemia, Experimental / Q000235:genetics*; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000009:adverse effects*; D009153:Mutagens / Q000494:pharmacology; D013937:Thymidine Kinase / Q000172:deficiency*
D008937:Mitomycins; D009153:Mutagens; D002110:Caffeine; D016685:Mitomycin; D013937:Thymidine Kinase