Cigarette smoke condensate induces cytochromes P450 and aldo-keto reductases in oral cancer cells.
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 (25microg/ml for 24h) 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.
Nagaraj
Nagathihalli S
NS
Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Delia Baxter Bldg. 321F, 580 South Preston Street, Louisville, KY 40202, USA.
Beckers
Simone
S
Mensah
John K
JK
Waigel
Sabine
S
Vigneswaran
Nadarajah
N
Zacharias
Wolfgang
W
D000368:Aged; D000429:Alcohol Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*
D012333:RNA, Messenger; D012906:Smoke; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase