Prevention of the areca nut extract-induced unscheduled DNA synthesis of gingival keratinocytes by vitamin C and thiol compounds
Journal
Oral Oncology
Journal Volume
38
Journal Issue
3
Pages
258-265
Date Issued
2002
Author(s)
Abstract
There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is the major risk factor of oral cancer in India, Taiwan, South Africa and numerous other countries. Areca nut (AN) extract, the main component of BQ, exerts cytotoxicity and genotoxicity to several types of cells. In the present study, AN extract induced the unscheduled DNA synthesis (UDS) of gingival keratinocytes (GK). Vitamin C, at concentration of 50 and 200 μg/ml prevented the AN-induced UDS by 41 and 56%, respectively. Glutathione (GSH, 1-3 mM) and N-acetyl-L-cysteine (NAC, 1-3 mM) also protected the AN-induced UDS by 89-100 and 76-90%. These preventive effects were not due to cytotoxicity as analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Deferoxamine (20 and 30 mM), an iron chelator and a free radical scavenger, also prevented AN extract induced UDS of GK by 30-55%. On the contrary, banthocuproine (50-200 μM, a copper chelator) and 1,10-phenanthroline (50, 100 μM, a lipid permeable iron chelator), lacked preventive effects. Specific reactive oxygen species scavengers such as dimethyl-sulfoxide (2%), mannitol (10-20 mM), dimethylthiourea (10-20 mM), pyruvate (10 mM), catalase (200 and 400 U/ml), and superoxide dismutase (50 and 200 U/ml) also lacked these preventive effects. Moreover, higher concentrations of H2O2 (0.5-1 mM) inhibited the basal levels of UDS by 19-37%. Interestingly, NAC, GSH, Vitamin C and deferoxamine cannot prevent the AN-induced morphological changes of GK at similar concentrations. These results reveal that AN extract-induced UDS of GK is associated with free radical reactions. Possibly different ingredients of AN is responsible for genotoxicity and cytotoxicity. Vitamin C, GSH and NAC may be potentially used in the future for chemoprevention of BQ chewing related oral mucosal lesions. ? 2002 Elsevier Science Ltd. All rights reserved.
SDGs
Other Subjects
1,10 phenanthroline; 3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide; acetylcysteine; ascorbic acid; banthocuproine; catalase; deferoxamine; dimethyl sulfoxide; dimethylthiourea; free radical; glutathione; hydrogen peroxide; iron chelating agent; mannitol; pyruvic acid; reactive oxygen metabolite; scavenger; superoxide dismutase; thiol derivative; unclassified drug; antineoplastic activity; article; betel nut; cancer prevention; cell protection; chemoprophylaxis; concentration response; controlled study; cytotoxicity; drug effect; genotoxicity; gingiva; human; human cell; human tissue; keratinocyte; mastication; mouth carcinoma; priority journal; unscheduled DNA synthesis; Antioxidants; Areca; Ascorbic Acid; Cells, Cultured; Chelating Agents; Deferoxamine; DNA; Gingiva; Humans; Keratinocytes; Mouth Neoplasms; Plant Extracts; Sulfhydryl Compounds
Type
journal article