N-acetyl-L-cysteine prevents DNA damage induced by UVA, UVB and visible radiation in human fibroblasts

被引:56
作者
Morley, N [1 ]
Curnow, A [1 ]
Salter, L [1 ]
Campbell, S [1 ]
Gould, D [1 ]
机构
[1] Publ Hlth Labs Project, Cornwall Dermatol Res, Cornwall TR1 3LQ, England
关键词
N-acetylcysteine; glutathione; buthionine sulfoximine; ultraviolet radiation; reactive oxygen species; HUMAN SKIN FIBROBLASTS; GLUTATHIONE; CELLS; ANTIOXIDANTS; SENSITIVITY; MECHANISMS; CANCER;
D O I
10.1016/j.jphotobiol.2003.06.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The thiol N-acetyl-L-cysteine (NAC) is a source of cysteine for the synthesis of the endogenous antioxidant glutathione (GSH) which is depleted by ultraviolet radiation. It is also associated with the scavenging of reactive oxygen species (ROS). In this study the effects of NAC were examined in cultured human fibroblasts during prolonged exposure to ultraviolet B (UVB), ultraviolet A (UVA) and visible irradiation (280-700 nm), delivered by a 150 W xenon-arc lamp. The alkaline comet assay was used to assess the DNA damage in individual cells. It was found that incubating skin and lung fibroblasts at 37 degreesC for I h with an optimal 6 mM NAC supplement prior to light exposure, significantly reduced the level of DNA damage in both cell types, however, the skin fibroblasts were less sensitive to xenon-arc lamp irradiation than lung fibroblasts. NAC incubation resulted in an initial delay in DNA damage when the cells were irradiated. There was also a significant reduction in the overall levels of DNA damage observed with continued irradiation. NAC significantly reduced the DNA damage produced in lung fibroblasts depleted of normal GSH protection by the glutamylcysteinyl synthetase inhibitor, L-buthionine-[S,R]-sulfoximine. Although the specific mechanism of NAC protection has not yet been elucidated, these results support the hypothesis that NAC may protect the cells directly, by scavenging ROS induced by UVA and visible radiation, and indirectly by donating cysteine for GSH synthesis. (C) 2003 Published by Elsevier B.V.
引用
收藏
页码:55 / 60
页数:6
相关论文
共 25 条
[1]  
Anderson M E, 1997, Adv Pharmacol, V38, P65
[2]   ENDOGENOUS GLUTATHIONE LEVELS MODULATE THE FREQUENCY OF BOTH SPONTANEOUS AND LONG WAVELENGTH ULTRAVIOLET INDUCED MUTATIONS IN HUMAN-CELLS [J].
APPLEGATE, LA ;
LAUTIER, D ;
FRENK, E ;
TYRRELL, RM .
CARCINOGENESIS, 1992, 13 (09) :1557-1560
[3]  
Armstrong B K, 1997, Australas J Dermatol, V38 Suppl 1, pS1
[4]  
Cadet J, 1997, BIOL CHEM, V378, P1275
[5]   Intracellular antioxidants:: from chemical to biochemical mechanisms [J].
Chaudière, J ;
Ferrari-Iliou, R .
FOOD AND CHEMICAL TOXICOLOGY, 1999, 37 (9-10) :949-962
[6]   GLUTATHIONE EXPORT BY HUMAN LYMPHOID-CELLS - DEPLETION OF GLUTATHIONE BY INHIBITION OF ITS SYNTHESIS DECREASES EXPORT AND INCREASES SENSITIVITY TO IRRADIATION [J].
DETHMERS, JK ;
MEISTER, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (12) :7492-7496
[7]   Thiols and selenium: protective effect on human skin fibroblasts exposed to UVA radiation [J].
Emonet, N ;
Leccia, MT ;
Favier, A ;
Beani, JC ;
Richard, MJ .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1997, 40 (01) :84-90
[8]   Protective effects of antioxidants against UVA-induced DNA damage in human skin fibroblasts in culture [J].
Emonet-Piccardi, N ;
Richard, MJ ;
Ravanat, JL ;
Signorini, N ;
Cadet, J ;
Béani, JC .
FREE RADICAL RESEARCH, 1998, 29 (04) :307-313
[9]  
Friedberg E.C., 1995, DNA REPAIR MUTAGENES
[10]   How nucleotide excision repair protects against cancer [J].
Friedberg, EC .
NATURE REVIEWS CANCER, 2001, 1 (01) :22-33