title: [Metabolic activation of benzo(a)pyrene enhanced transformation of human bronchial epithelium cell HBETR].
abstract: OBJECTIVE
  To study the application of different metabolic activation systems in benzo(a)pyrene [B(a)P]-induced human bronchial epithelium cell HBETR transformation.
  
  
  METHODS
  In vitro metabolic activations of B(a)P were compared with rat liver S9 fraction mix, overexpression of a key enzyme (P450 CYP1A1), and prior low dose B(a)P (1 micromol/L) induction. Using soft agar assay and tumorigenicity assay, the different metabolic activation systems were compared to the influence on transformation of human bronchial epithelium cell HBETR.
  
  
  RESULTS
  Both immunoblotting and enzyme activity showed that cells overexpressing CYP1A1 (HBETR-1A1) and 48 h after low dose B(a)P induction (HBETR-IN) had high-level expression of CYP1A1. There were no obvious changes in the biology characteristic of these cells. The latencies of cell transformation in HBETR-1A1 and HBETR-IN cells were 11 weeks when cells were treated with B(a)P at concentration of 20 micromol/L, while it took 14 weeks to achieve cell transformation in their control cells. The latencies of malignant transformation in HBETR cells in presence or absence of S9-mix were 14 weeks and 20 weeks, respectively. The efficiencies of cell transformation were in consonance with the protein level of endogenous CYP1A1 enzyme and its enzyme activity.
  
  
  CONCLUSIONS
  The three metabolic conditions of the addition of rat liver S9 fraction mix, overexpression of a key enzyme (CYP1A1), and low dose B(a) P induction could enhance the B(a)P metabolic activation and shorten the latency of malignant transformation. In terms of the feasibility, difficulty of manipulation, stability, and reliability, low dose B(a)P induction could seem to be a prospective system used in metabolic activation in comparison with rat liver S9 fraction mix addition.
authors.affiliation: Faculty of Preventive Medicine, School of Public Health, Sun-Yat Sen University, Guangzhou 510080, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Pang
authors.forename: Yandong
authors.initials: Y
authors.lastname: Lai
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xiao
authors.forename: Wenxue
authors.initials: W
authors.lastname: Li
authors.forename: Rulin
authors.initials: R
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wei
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Lin
authors.forename: Daochuan
authors.initials: D
authors.lastname: Li
authors.forename: Shifu
authors.initials: S
authors.lastname: Tang
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Li
authors.forename: Dawei
authors.initials: D
authors.lastname: Wu
authors.forename: Zhongning
authors.initials: Z
authors.lastname: Lin
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
mesh_terms: D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity*; D001711:Biotransformation / Q000187:drug effects* / Q000235:genetics; D001980:Bronchi / Q000166:cytology*; D015197:Carcinogenicity Tests / Q000379:methods; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans
chemical_list: D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1