Effect of N-acetylcysteine on UVB-induced apoptosis and DNA repair in human and mouse keratinocytes.
The incidence of skin cancer is increasing rapidly, particularly in the Caucasian population. Epidemiological and experimental studies demonstrated that ultraviolet radiation (UVR) is the primary cause for the increasing incidence of skin cancer. It is well known that UV irradiation induces DNA damage. If the damage is not repaired or removed in time, it can lead to mutations and skin carcinogenesis. N-acetylcysteine (NAC) has been shown to be an effective protector against UVB-induced immunosuppression and to modulate the expression of some oncogenes and tumor suppressor genes. To test further the protective effect of NAC against UVR, we used both in vitro and in vivo models to investigate the effect of NAC on UVB-induced apoptosis and repair of DNA damage in human and mouse keratinocytes. Our data indicate that the intracellular glutathione level was increased after treatment with NAC at 10-20 mM but decreased with 40 mM NAC treatment due to the toxicity. At concentrations up to 20 mM NAC did not have a significant effect on UVB-induced apoptosis of cultured human keratinocytes. In addition, in an in vivo mouse model, topical application of NAC (3 mumol cm-2) that has been shown to inhibit UVB-induced immunosuppression did not have any effect on UVB-induced apoptosis and did not reduce the formation or enhance the repair of UVB-induced cyclobutane pyrimidine dimers and (6-4) photoproducts. Our results indicate that NAC is ineffective in preserving the genomic stability of keratinocytes against UVB irradiation.
Bush
J A
JA
Department of Medicine, Vancouver Hospital and Health Science Centre, University of British Columbia, Canada.
Ho
V C
VC
Mitchell
D L
DL
Tron
V A
VA
Li
G
G
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D014466:Ultraviolet Rays
D004247:DNA; D005978:Glutathione; D000111:Acetylcysteine