Cigarette smoke condensate induces cytochromes P450 and aldo-keto reductases in oral cancer cells

Nagathihalli S. Nagaraj, Simone Beckers, John K. Mensah, Sabine Waigel, Nadarajah Vigneswaran, Wolfgang Zacharias

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Our objective is to identify molecular factors which contribute to the increased risk of smokers for oral squamous cell carcinoma (OSCC). In the present study, we investigated the effects of cigarette smoke condensate (CSC) on gene expression profiles in different human oral cell phenotypes: normal epidermal keratinocytes (NHEK), oral dysplasia cell lines (Leuk1 and Leuk2), and a primary oral carcinoma cell line (101A). We determined differential gene expression patterns in CSC-exposed versus non-exposed cells using high-density microarray RNA expression profiling and validation by quantitative real-time RT-PCR. A set of 35 genes was specifically up- or down-regulated following CSC treatment (25 μg/ml for 24 h) by at least 2-fold in any one cell type. Notably, five genes of the cytochrome P450 (CYP1A1, CYP1B1) and aldo-keto reductase (AKR1C1, AKR1C3, AKR1B10) families were highly increased in expression, some of them 15- to 30-fold. The timing and extent of induction for these genes differed among the four cell phenotypes. A potential biological interaction network for the CSC response in oral cells was derived from these data, proposing novel putative response pathways. These CSC-responsive genes presumably participate in the prevention or repair of carcinogen-induced DNA damage in tobacco-related oral carcinogenesis, and may potentially be exploited for determining the severity of exposure and for correcting mutagenic damage in exposed tissues of the oral cavity.

Original languageEnglish (US)
Pages (from-to)182-194
Number of pages13
JournalToxicology Letters
Volume165
Issue number2
DOIs
StatePublished - Aug 20 2006
Externally publishedYes

Keywords

  • Aldo-keto reductases
  • Cigarette smoke condensate
  • Cytochrome P450
  • Gene expression
  • Microarray
  • Oral cancer

ASJC Scopus subject areas

  • Toxicology

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