Correspondence between effects of 5-azacytidine on SCE formation, cell cycling and DNA methylation in Chinese hamster cells.
The effects of 5-azacytidine (5-Aza-C), alone and in combination with mitomycin C, were measured on sister-chromatid exchange (SCE) formation and DNA methylation in different genomic regions of Chinese hamster ovary cells and in Chinese hamster cells containing amplified, dihydrofolate reductase sequences and resistant to methotrexate. 5-Aza-C, when present for the penultimate preharvest cell cycle, induced SCEs in a manner consistent with a directly measured reduction in deoxycytosine methylation in cellular DNA. At higher 5-Aza-C concentrations, cell cycling was inhibited and both SCE induction and DNA demethylation tended to level off. Under appropriate conditions, 5-Aza-C also potentiated the induction of SCEs by mitomycin C. 5-Aza-C-induced DNA demethylation could also be detected in the vicinity of different DNA sequences with the use of comparative HpaII/MspI digestion, DNA blotting, and molecular probes. The efficiency of an individual demethylation event in inducing SCE induction appeared to be very low, compared with alkylating agents such as 8-methoxypsoralen, suggesting that SCE induction by 5-Aza-C might be an indirect effect from long range changes induced in cellular DNA or chromatin conformation.
Shipley
J
J
Sakai
K
K
Tantravahi
U
U
Fendrock
B
B
Latt
S A
SA
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D008745:Methylation; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D010053:Ovary; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D008937:Mitomycins; D016685:Mitomycin; D003596:Cytosine; D004247:DNA; D001374:Azacitidine