Sister chromatid exchanges induced by DNA demethylating agents persist through several cell cycles in mammalian cells.
Eukaryotic DNA methylation has been extensively studied in recent years. The ability of many carcinogens to interfere with DNA methylation has not yet been directly related to their tumorigenic activity. Recent data obtained using L-ethionine and 5-azacytidine--both demethylating agents--showed a small but significant increase in the sister chromatid exchange (SCE) rate induced in mammalian cells (human lymphocytes and CHO cells). In this paper we show that the SCE increase induced by both these agents in Chinese hamster ovary (CHO) cells persists for as long as 10 cell cycles. On the other hand mitomycin-C and u.v. light-induced SCEs show a rapid decrease to the control value, as reported for all known SCE inducers. We suggest that DNA demethylation and SCEs are connected through a perturbation of the cell machinery at the level of the replication fork, producing an increase of the error-prone ligation. Since the methylation level is maintained (inherited), the SCE increase produced by these recombinational events will not be corrected through several cell cycles.
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002453:Cell Cycle; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism*; D005001:Ethionine / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D012854:Sister Chromatid Exchange; D014466:Ultraviolet Rays
D008937:Mitomycins; D016685:Mitomycin; D004247:DNA; D001374:Azacitidine; D005001:Ethionine