Effect of L-ethionine on spontaneous and MMC-induced SCEs in G0 and G1 human lymphocytes under liquid-holding recovery conditions.
L-Ethionine is an ethyl analogue of the amino acid, methionine, well known as a carcinogen but not as a mutagen. Its activity is clearly related to its capacity to hypomethylate DNA and RNA. At a final concentration of 5 mM, L-ethionine completely inhibits DNA synthesis in PHA-stimulated human lymphocytes, probably acting on a methylation reaction critical for the initiation of the S phase. This block can be reversed. Utilizing this capacity of L-ethionine to block cell proliferation, we have studied the influence of G0 and G1 repair of premutational damage (PMD) (equivalent to liquid-holding recovery in bacteria) on spontaneous and MMC-induced SCEs in human lymphocytes. Our results clearly show that L-ethionine in our experimental conditions significantly increases the frequencies of spontaneous and MMC-induced SCEs. In view of the hypomethylating activity of the analogue, we hypothesize that this action at the replication fork level may increase the error-prone ligation of unrepaired lesions, thus influencing the frequency of occurrence of SCEs.
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D046508:Culture Techniques / Q000379:methods; D005001:Ethionine / Q000494:pharmacology*; D006801:Humans; D007399:Interphase / Q000187:drug effects*; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008297:Male; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; D016685:Mitomycin; D005001:Ethionine