Proliferation-dependent reduction of sister-chromatid exchange frequency induced by mitomycin C in human lymphoblastoid cells and its suppression by inhibitors of DNA replication.
A high frequency of sister-chromatid exchange (SCE) induced in cells of a human lymphoblastoid cell line, NL3, by 2-h treatment with 1 microM mitomycin C (MMC) was maintained after holding the treated cells in a nonproliferating state for 48 h before cells were transferred into the BrdUrd-containing medium for SCE assay. The same was observed in cells treated with 4-nitroquinoline 1-oxide (4NQO) or ethyl methanesulfonate (EMS). In contrast, when MMC-treated cells were transferred into a growth medium and allowed to proliferate for various periods of time before SCE assay, MMC-induced SCE frequency decreased with time and reached near control level after 48 h. The reduction in SCE was also observed in 4NQO-treated cells, though to a lesser extent, but not in EMS-treated cells. When hydroxyurea or 1-beta-D-arabinofuranosylcytosine was given as a post-MMC treatment during this recovery process, such a reduction of SCE frequency was suppressed and the extent of the suppression appears to be roughly parallel to their ability to inhibit DNA replication. Cycloheximide and 5-azacytidine also exerted a similar inhibitory effect on the reduction of SCE. Benzamide and caffeine had no appreciable effect. Our results indicate that the SCE-forming lesions induced by MMC can be eliminated only in proliferating cells, probably during DNA replication.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D002455:Cell Division; D003513:Cycloheximide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D003864:Depression, Chemical; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D008937:Mitomycins; D003561:Cytarabine; D016685:Mitomycin; D015112:4-Nitroquinoline-1-oxide; D003513:Cycloheximide; D005020:Ethyl Methanesulfonate; D006918:Hydroxyurea