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Ascorbic acid‐dehydroascorbate induces cell cycle arrest at G 2 /M DNA damage checkpoint during oxidative stress
Author(s) -
Bijur Gautam N.,
Briggs Bruce,
Hitchcock Charles L.,
Williams Marshall V.
Publication year - 1999
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1999)33:2<144::aid-em6>3.0.co;2-v
Subject(s) - ascorbic acid , oxidative stress , cell cycle checkpoint , dna damage , cell cycle , chek1 , g2 m dna damage checkpoint , microbiology and biotechnology , dna repair , reactive oxygen species , chemistry , cyclin dependent kinase 1 , biology , apoptosis , biochemistry , dna , food science
Reactive oxygen species induce cellular damage and have been implicated as mediators for cellular signaling pathways. However, a linkage between the cellular redox status and cell cycle progression has not been demonstrated. We previously demonstrated, using the Chinese hamster ovary cell line AS52, that the cytotoxic and mutagenic effects of oxidative stress is prevented by ascorbic acid (AA), but only when cells are treated with AA prior to treatment with the stressor. To elucidate the mechanism(s) responsible for this effect, we determined the effect of AA on cell cycle progression during oxidative stress. Flow cytometric analyses demonstrated that treatment of AS52 cells with AA (50 μM), prior to treatment with a radical generating system (RGS), enhanced cell cycle arrest at the G 2 /M DNA damage checkpoint when compared to cells treated with RGS. AA had no effect on cell cycle progression in the absence of oxidative stress. Furthermore, under conditions that prevent the reduction of dehydroascorbate (DHA), the oxidized form of AA, cell cycle arrest was also induced at the G 2 /M DNA damage checkpoint. These observations demonstrate that during periods of oxidative stress, AA functions as an antioxidant and DHA enhances transient arrest at the G 2 /M checkpoint by delaying the activation of cyclin B‐cdc2. These results suggest the presence of a unique redox mechanism for the regulation of cell cycle progression and also demonstrate a novel mechanism by which AA protects cells from damage due to oxidative stress. Environ. Mol. Mutagen. 33:144–152, 1999 © 1999 Wiley‐Liss, Inc.