title: Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells.
abstract: The International Agency for Research on Cancer lists the principal component of betel quid (BQ), the areca nut, and that of cigarette smoke, benzo[a]pyrene (BaP), as Group 1 carcinogens. Epidemiological studies have shown that coexposure of BQ and cigarette smoke markedly increases the risk of cancer. We previously demonstrated that arecoline, the most abundant alkaloid in the areca nut, inhibits nucleotide excision repair through the repression of p53 activity. To investigate the combined potency of arecoline and BaP in carcinogenesis, we treated human epithelial HEp-2 cells with subcytotoxic doses of arecoline and BaP, alone or in combination, and examined the effects on DNA damage and repair. When exposed for 24h, BaP enhanced DNA repair and p53 transactivation activity. However, these enhancements were suppressed through concurrent treatment of the cells with arecoline. Using a Comet assay, we found that extended exposure to arecoline and BaP caused moderate-to-severe DNA damage in 60% of the cells. Expression of the XPD helicase was transcriptionally suppressed by 1 week of treatment with BaP. Our studies have revealed potential targets in the DNA repair pathway that are affected by BQ and tobacco components, as well as the effect of these components on carcinogenesis.
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, 71101, Tainan, Taiwan. Electronic address: jaulingh@mail.cjcu.edu.tw.
authors.forename: J L
authors.initials: JL
authors.lastname: Huang
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, 71101, Tainan, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 80708, Kaohsiung, Taiwan.
authors.forename: H H
authors.initials: HH
authors.lastname: Lu
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, 71101, Tainan, Taiwan.
authors.forename: Y N
authors.initials: YN
authors.lastname: Lu
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, 71101, Tainan, Taiwan.
authors.forename: P S
authors.initials: PS
authors.lastname: Hung
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 80708, Kaohsiung, Taiwan.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, 71101, Tainan, Taiwan.
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, 71101, Tainan, Taiwan.
authors.forename: C C
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, 71101, Tainan, Taiwan.
authors.forename: T Y
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, 71101, Tainan, Taiwan.
authors.forename: S Y
authors.initials: SY
authors.lastname: Lu
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 80708, Kaohsiung, Taiwan; Department of Biological Sciences, National Sun Yat-sen University, 80424, Kaohsiung, Taiwan. Electronic address: changshenlin@gmail.com.
authors.forename: C S
authors.initials: CS
authors.lastname: Lin
mesh_terms: D001115:Arecoline / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans
chemical_list: D002273:Carcinogens; D001564:Benzo(a)pyrene; D001115:Arecoline
keywords: Arecoline; Benzo[a]pyrene; DNA damage; DNA repair; XPD; p53