N-acetyl cysteine protects against ionizing radiation-induced DNA damage but not against cell killing in yeast and mammals.
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 gamma-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 gamma-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 gamma-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 1Gy but not with 4Gy. 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.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Ramune
R
Reliene
Julianne M
JM
Pollard
Zhanna
Z
Sobol
Benedicte
B
Trouiller
Richard A
RA
Gatti
Robert H
RH
Schiestl
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D003114:Colony-Forming Units Assay; D020552:Comet Assay; D053960:DNA Breaks; D004249:DNA Damage; D016166:Free Radical Scavengers / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*
D016166:Free Radical Scavengers; C468783:H2AX protein, human; D006657:Histones; D000111:Acetylcysteine