TY - JOUR
T1 - N-acetyl cysteine protects against ionizing radiation-induced DNA damage but not against cell killing in yeast and mammals
AU - Reliene, Ramune
AU - Pollard, Julianne M.
AU - Sobol, Zhanna
AU - Trouiller, Benedicte
AU - Gatti, Richard A.
AU - Schiestl, Robert H.
N1 - Funding Information:
We are grateful to Jenny Kotlerman from the Department of Medicine Statistics Core UCLA School of Medicine for statistical analysis of the Comet assay data. Francesca Fike performed colony survival assay. Kurt Hafer calculated the radiation dose rate for yeast experiments. The authors wish to thank members of the Schiestl lab for comments on the manuscript. This research was supported by NIH U19 AI 67769-01 to RHS and RAG and NIH 1RO3 CA133928-01 to RR.
PY - 2009/6/1
Y1 - 2009/6/1
N2 - Ionizing radiation (IR) induces DNA strand breaks leading to cell death or deleterious genome rearrangements. In the present study, we examined the role of N-acetyl-L-cysteine (NAC), a clinically proven safe agent, for it's ability to protect against γ-ray-induced DNA strand breaks and/or DNA deletions in yeast and mammals. In the yeast Saccharomyces cerevisiae, DNA deletions were scored by reversion to histidine prototrophy. Human lymphoblastoid cells were examined for the frequency of γ-H2AX foci formation, indicative of DNA double strand break formation. DNA strand breaks were also measured in mouse peripheral blood by the alkaline comet assay. In yeast, NAC reduced the frequency of IR-induced DNA deletions. However, NAC did not protect against cell death. NAC also reduced γ-H2AX foci formation in human lymphoblastoid cells but had no protective effect in the colony survival assay. NAC administration via drinking water fully protected against DNA strand breaks in mice whole-body irradiated with 1 Gy but not with 4 Gy. NAC treatment in the absence of irradiation was not genotoxic. These data suggest that, given the safety and efficacy of NAC in humans, NAC may be useful in radiation therapy to prevent radiation-mediated genotoxicity, but does not interfere with efficient cancer cell killing.
AB - Ionizing radiation (IR) induces DNA strand breaks leading to cell death or deleterious genome rearrangements. In the present study, we examined the role of N-acetyl-L-cysteine (NAC), a clinically proven safe agent, for it's ability to protect against γ-ray-induced DNA strand breaks and/or DNA deletions in yeast and mammals. In the yeast Saccharomyces cerevisiae, DNA deletions were scored by reversion to histidine prototrophy. Human lymphoblastoid cells were examined for the frequency of γ-H2AX foci formation, indicative of DNA double strand break formation. DNA strand breaks were also measured in mouse peripheral blood by the alkaline comet assay. In yeast, NAC reduced the frequency of IR-induced DNA deletions. However, NAC did not protect against cell death. NAC also reduced γ-H2AX foci formation in human lymphoblastoid cells but had no protective effect in the colony survival assay. NAC administration via drinking water fully protected against DNA strand breaks in mice whole-body irradiated with 1 Gy but not with 4 Gy. NAC treatment in the absence of irradiation was not genotoxic. These data suggest that, given the safety and efficacy of NAC in humans, NAC may be useful in radiation therapy to prevent radiation-mediated genotoxicity, but does not interfere with efficient cancer cell killing.
KW - DNA deletions
KW - DNA strand breaks
KW - Genotoxicity
KW - Ionizing radiation
KW - N-acetyl cysteine
KW - γ-H2AX foci
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U2 - 10.1016/j.mrfmmm.2009.02.016
DO - 10.1016/j.mrfmmm.2009.02.016
M3 - Article
C2 - 19427509
AN - SCOPUS:67349122279
SN - 0027-5107
VL - 665
SP - 37
EP - 43
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -