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.

[1]  N. Palackal,et al.  Activation of Polycyclic Aromatic Hydrocarbontrans-Dihydrodiol Proximate Carcinogens by Human Aldo-keto Reductase (AKR1C) Enzymes and Their Functional Overexpression in Human Lung Carcinoma (A549) Cells* , 2002, The Journal of Biological Chemistry.

[2]  J. Sudbø,et al.  Retracted: The evolution of predictive oncology and molecular‐based therapy for oral cancer prevention , 2005, International journal of cancer.

[3]  T. Flynn,et al.  The aldo-keto reductases and their role in cancer. , 1999, Advances in experimental medicine and biology.

[4]  R. Tukey,et al.  The catalytic activity of four expressed human cytochrome P450s towards benzo[a]pyrene and the isomers of its proximate carcinogen. , 1993, Biochemical and biophysical research communications.

[5]  T. Brüning,et al.  Cytochrome P450 1B1, a new keystone in gene–environment interactions related to human head and neck cancer? , 2002, Archives of Toxicology.

[6]  P. Strickland,et al.  Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by human cytochrome P4501B1. , 1997, Carcinogenesis.

[7]  D. Nebert.  Role of genetics and drug metabolism in human cancer risk. , 1991, Mutation research.

[8]  S. Neuhausen,et al.  CYP1A1, cigarette smoking, and colon and rectal cancer. , 2004, American journal of epidemiology.

[9]  H. Yamazaki,et al.  Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. , 1999, Drug metabolism and disposition: the biological fate of chemicals.

[10]  F. Curriero,et al.  Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers. , 2004, Toxicology and applied pharmacology.

[11]  Hiroyuki Aburatani,et al.  Overexpression of the Aldo-Keto Reductase Family Protein AKR1B10 Is Highly Correlated with Smokers' Non–Small Cell Lung Carcinomas , 2005, Clinical Cancer Research.

[12]  T. Penning,et al.  Aldo-keto reductases and formation of polycyclic aromatic hydrocarbon o-quinones. , 2004, Methods in enzymology.

[13]  Michael E. Burczynski,et al.  Human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1–AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones , 2000 .

[14]  J. H. Kim,et al.  Metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-diol by human cytochrome P450 1B1. , 1998, Carcinogenesis.

[15]  T. Shimada,et al.  Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and1B1 , 2004, Cancer science.

[16]  D. Nebert,et al.  Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis. , 2000, Biochemical pharmacology.

[17]  C. Kiyohara,et al.  CYP1A1 inducing potential of airborne particulate extracts collected during a 25-year period (1975-2000). , 2005, Asian Pacific journal of cancer prevention : APJCP.

[18]  W. Thilly,et al.  Quantitative RT-PCR measurement of cytochromes p450 1A1, 1B1, and 2B7, microsomal epoxide hydrolase, and NADPH oxidoreductase expression in lung cells of smokers and nonsmokers. , 1997, American journal of respiratory cell and molecular biology.

[19]  Trevor M Penning,et al.  Competing roles of cytochrome P450 1A1/1B1 and aldo-keto reductase 1A1 in the metabolic activation of (+/-)-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene in human bronchoalveolar cell extracts. , 2005, Chemical research in toxicology.

[20]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[21]  S. Shehin,et al.  Transcriptional Regulation of the Human CYP1B1 Gene , 2000, The Journal of Biological Chemistry.

[22]  J. Whitlock,et al.  Induction of cytochrome P4501A1. , 1999, Annual review of pharmacology and toxicology.

[23]  J. Field,et al.  Reactive oxygen species generated by PAH o-quinones cause change-in-function mutations in p53. , 2002, Chemical research in toxicology.

[24]  A. Rannug,et al.  Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1: a study on host factors in relation to age at onset, gender and histological cancer types. , 1994, Carcinogenesis.

[25]  Trevor M Penning,et al.  AKR1B10: A New Diagnostic Marker of Non–Small Cell Lung Carcinoma in Smokers , 2005, Clinical Cancer Research.

[26]  W. F. Greenlee,et al.  Regulation, function, and tissue-specific expression of cytochrome P450 CYP1B1. , 2001, Annual review of pharmacology and toxicology.

[27]  N. Altorki,et al.  Benzo[a]pyrene phenols are more potent inducers of CYP1A1, CYP1B1 and COX-2 than benzo[a]pyrene glucuronides in cell lines derived from the human aerodigestive tract. , 2003, Carcinogenesis.

[28]  T. Walle,et al.  Preferential induction of CYP1B1 by benzo[a]pyrene in human oral epithelial cells: impact on DNA adduct formation and prevention by polyphenols. , 2005, Carcinogenesis.

[29]  H. Bartsch,et al.  Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[30]  H. Rubin.  Synergistic mechanisms in carcinogenesis by polycyclic aromatic hydrocarbons and by tobacco smoke: a bio-historical perspective with updates. , 2001, Carcinogenesis.

[31]  N. Palackal,et al.  The Reactive Oxygen Species- and Michael Acceptor-inducible Human Aldo-Keto Reductase AKR1C1 Reduces the α,β-Unsaturated Aldehyde 4-Hydroxy-2-nonenal to 1,4-Dihydroxy-2-nonene* , 2000, The Journal of Biological Chemistry.

[32]  C. Scully,et al.  Tobacco, oral cancer, and treatment of dependence. , 2005, Oral oncology.

[33]  B. Mahadevan,et al.  Altered gene expression patterns in MCF-7 cells induced by the urban dust particulate complex mixture standard reference material 1649a. , 2005, Cancer research.

[34]  F. Guengerich.  Metabolism of chemical carcinogens. , 2000, Carcinogenesis.

[35]  N. Altorki,et al.  Tobacco smoke induces CYP1B1 in the aerodigestive tract. , 2004, Carcinogenesis.

[36]  D. Nebert,et al.  Metabolism of polycyclic aromatic hydrocarbons: etiologic role in carcinogenesis. , 1982, Pharmacological reviews.

[37]  H. Yamazaki,et al.  Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. , 1996, Cancer research.

[38]  K. Keyomarsi,et al.  Expression of cytochromes P450 in human breast tissue and tumors. , 1996, Drug metabolism and disposition: the biological fate of chemicals.

[39]  Allan B. Okey,et al.  Role of Aryl Hydrocarbon Receptor-mediated Induction of the CYP1 Enzymes in Environmental Toxicity and Cancer* , 2004, Journal of Biological Chemistry.