Effects of N-acetyl-L-cysteine and ascorbic acid on mutagen-induced chromosomal sensitivity in patients with head and neck cancers.
The protective effect of N-acetyl-L-cysteine (NAC) and ascorbic acid on mutagen-induced chromosomal breakage was determined using human lymphoblastoid cell lines as well as freshly cultured lymphocytes from patients with head and neck malignancies and healthy control subjects. Mutagen sensitivity was determined using the previously described bleomycin exposure assay. The toxicities of different concentrations of NAC and ascorbic acid, as well as both the preincubation and dose-dependent protective effects of these two agents, were analyzed. Both test drugs proved to be effective in diminishing mutagen-induced chromatid breakage in established lymphocyte cell lines. In freshly cultured lymphocytes, NAC given in doses ranging from 0.1 to 10 mmol/L decreased the number of mutagen-induced breaks per cell in a range from 23% to 73%, and ascorbic acid decreased chromosomal breakage by 21% to 58% in a dose range from 0.01 to 1 mmol/L. The results of this study demonstrate the protective effect mediated in vitro by both NAC and ascorbic acid against mutagen-induced chromosomal damage. A similar in vivo phenomenon may explain the differences in occurrence of head and neck cancer between populations with different dietary backgrounds.
Trizna
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Department of Head and Neck Surgery, University of Texas M. D. AndersonCancer Center, Houston.
Schantz
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Hsu
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D000111:Acetylcysteine / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001761:Bleomycin / Q000633:toxicity; D002460:Cell Line; D002873:Chromosome Fragility; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000517:prevention & control; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured
D001761:Bleomycin; D001205:Ascorbic Acid; D000111:Acetylcysteine