Inhibition of post-replication repair of alkylated DNA by caffeine in Chinese hamster cells but not HeLa cells |
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Authors: | J J Roberts K N Ward |
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Institution: | Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, Fulham Road, London SW3 6JB Great Britain |
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Abstract: | Caffeine has been found to potentiate the lethal effects of sulphur mustard (SM) and N-methyl-N-nitrosourea (MNU) in a line of Chinese hamster cells but not in a line of HeLa cells. The sensitization of SM-treated cells by caffeine was S phase specific, and persisted for up to 24 h after alkylation of asynchronous cell cultures. The sensitization of MNU-treated cells, however, was not S phase specific but persisted for up to 50 h after the initial alkylation. Possible explanations for this difference between these two types of alkylating agent were discussed. Previously, evidence was presented which suggested that the alkylation-induced delay in the time of the peak rate of DNA synthesis in Chinese hamster cells was associated with the operation of post-DNA replication repair mechanism in these cells. Caffeine has now been found to reverse this alkylation-induced delay of DNA synthesis in both SM- and MNU-alkylated Chinese hamster cells. It is therefore proposed that caffeine sensitizes alkylated cells by inhibition of a post-replication DNA repair mechanism. No support was obtained for the alternative possibility that caffeine inhibits alkylation-induced excision repair of damaged DNA. The role of DNA repair in the production of the lethal mutagenic and cytological effects of alkylating agents is discussed. |
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Keywords: | BUdR 5-bromo-2'-deoxyuridine MNU SM sulphur mustard TCA trichloroacetic acid TdR thymidine |
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