CELL-DEATH AND CELL-CYCLE PERTURBATION IN THE DEVELOPMENTAL TOXICITY OF THE DEMETHYLATING AGENT, 5-AZA-2'-DEOXYCYTIDINE
CELL-DEATH AND CELL-CYCLE PERTURBATION IN THE DEVELOPMENTAL TOXICITY OF THE DEMETHYLATING AGENT, 5-AZA-2'-DEOXYCYTIDINE
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DOI：
10.1002/tera.1420500504
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发表时间：
1994-11-01
期刊：
影响因子：
--
通讯作者：
CHERNOFF, N
中科院分区：
文献类型：
--
作者：
ROGERS, JM;FRANCIS, BM;CHERNOFF, N
DNA methylation is a probable mechanism for regulating gene expression, and alterations in methylation may significantly affect embryonic development. We administered the cytidine analogue 5-aza-2'-deoxycytidine (dAZA), a specific and potent demethylator of DNA, to pregnant mice to determine its teratogenicity and effects on embryonic cell death and cell cycle. Groups of females were dosed intraperitoneally on gestation day 10 with doses of 0.05-3 mg/kg dAZA and killed at 4, 8, or 28 hr later. Two embryos per litter were immediately stained with Nile blue sulfate (NBS) to identify areas of cell death; the remaining embryos were frozen and stored for subsequent flow cytometric (FCM) analysis of the cellular DNA synthetic cycle in limb buds. A dose-related accumulation of cells in the S and G(2)/M phases was observed at 4 and 8 hr after maternal dosing. S-phase accumulation was the most sensitive indicator of effect; a dose-related increase in the percentage of hindlimb bud cells in S-phase was evident at all dosages 4 hr after maternal dosing. By 28 hr postdosing, a normal cell cycle phase distribution was observed at doses of
