Combined antioxidant (β-carotene, α-tocopherol and ascorbic acid) supplementation increases the levels of lung retinoic acid and inhibits the activation of mitogen-activated protein kinase in the ferret lung cancer model

Dietary modulation of carcinogenesis-related pathwaysDietary item or component studied: b-carotene (BC), a-tocopherol (AT) and ascorbic acid (AA)Pathways studied: BC metabolism, activation of the MAP kinase pathway Study type (in vitro, animals, humans): male ferretsMode of exposure (if in vivo) (acute, chronic, root of exposure): 2diets, for 6 weeks and for 6 monthsImpact on pathway (including dose-response): ERK phosphorylation was significantly higher in SM + NNK treatment (_2.2-fold difference), as compared with the control or the AOX group (P<0.05)Compared with the control group or the AOX treated group, PCNA expression was significantly higher (36%) in the SM + NNK group (P<0.05)There was higher (50-63%) total p53 protein level in the group exposed to SM + NNK compared with the control group (P<0.05)p53 protein phosphorylation at serine-15 was higher in the groups exposed to SM + NNK (2-fold difference) (P<0.01), compared to controls.Bax protein expression was significantly higher (70%) in the SM + NNK group, compared with the control group (P<0.05. KEYWORDS CLASSIFICATION: alpha-Tocopherol;Aging;Agriculture;Animals;Antioxidants;Ascorbic Acid;bcl-2-Associated X Protein;beta Carotene;Biology;Blotting,Western;Boston;chemically induced;Carcinogens;Chromatography,High Pressure Liquid;drug effects;dietary modulation of carcinogenesis-related pathways;Dietary Supplements;Enzyme Activation;Ferrets;Immunohistochemistry;JNK Mitogen-Activated Protein Kinases;Lung;Lung Neoplasms;metabolism;Mitogen-Activated Protein Kinases;Nitrosamines;pathology;pharmacology;prevention & control;Proliferating Cell Nuclear Antigen;Research;Smoke;toxicity;Tobacco;Tobacco Smoke Pollution;Tretinoin;Tumor Suppressor Protein p53;United States.

[1]  A. Zhu,et al.  9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is accompanied by increased expression of RAR-beta but no change in cyclooxygenase-2. , 2006, Cancer letters.

[2]  R. Russell,et al.  Induction of pulmonary neoplasia in the smoke-exposed ferret by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): a model for human lung cancer. , 2006, Cancer letters.

[3]  J. Roy,et al.  A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. , 2005, Journal of the National Cancer Institute.

[4]  E. Fiala,et al.  Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E. , 2005, Carcinogenesis.

[5]  R. Price,et al.  c-Jun N-Terminal Kinase Contributes to Aberrant Retinoid Signaling in Lung Cancer Cells by Phosphorylating and Inducing Proteasomal Degradation of Retinoic Acid Receptor α , 2005, Molecular and Cellular Biology.

[6]  M. Lag,et al.  Role of cell signaling in B[a]P-induced apoptosis: characterization of unspecific effects of cell signaling inhibitors and apoptotic effects of B[a]P metabolites. , 2005, Chemico-biological interactions.

[7]  Deliang Tang,et al.  Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers. , 2005, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[8]  R. Russell,et al.  Low dose beta-carotene supplementation of ferrets attenuates smoke-induced lung phosphorylation of JNK, p38 MAPK, and p53 proteins. , 2004, The Journal of nutrition.

[9]  F. Khuri,et al.  Retinoids in lung cancer: friend, foe, or fellow traveler? , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  Xiang‐Dong Wang.  Carotenoid Oxidative/Degradative Products and Their Biological Activities , 2004 .

[11]  A. Mukherjee,et al.  Increased Susceptibility of Mice Lacking Clara Cell 10-kDa Protein to Lung Tumorigenesis by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a Potent Carcinogen in Cigarette Smoke* , 2004, Journal of Biological Chemistry.

[12]  Z. Li,et al.  Development of a comprehensive dietary antioxidant index and application to lung cancer risk in a cohort of male smokers. , 2004, American journal of epidemiology.

[13]  K. Yeh,et al.  Phosphorylation of p53 on Thr55 by ERK2 is necessary for doxorubicin-induced p53 activation and cell death , 2004, Oncogene.

[14]  R. Russell,et al.  α-Tocopherol and Ascorbic Acid Decrease the Production of β-Apo-carotenals and Increase the Formation of Retinoids from β-Carotene in the Lung Tissues of Cigarette Smoke–Exposed Ferrets In Vitro , 2004 .

[15]  C. Cross,et al.  5-nitro-γ-tocopherol increases in human plasma exposed to cigarette smoke in vitro and in vivo , 2003 .

[16]  R. Prywes,et al.  ATF1 Phosphorylation by the ERK MAPK Pathway Is Required for Epidermal Growth Factor-induced c-jun Expression* , 2002, The Journal of Biological Chemistry.

[17]  R. Russell,et al.  Retinoic acid inhibits hepatic Jun N-terminal kinase-dependent signaling pathway in ethanol-fed rats , 2002, Oncogene.

[18]  M. Ueno,et al.  Mechanism of p53-dependent Apoptosis Induced by 3-Methylcholanthrene , 2002, The Journal of Biological Chemistry.

[19]  Lucia Altucci,et al.  The promise of retinoids to fight against cancer , 2001, Nature Reviews Cancer.

[20]  Masamitsu Tanaka,et al.  Involvement of Alpha-PAK-Interacting Exchange Factor in the PAK1–c-Jun NH2-Terminal Kinase 1 Activation and Apoptosis Induced by Benzo[a]pyrene , 2001, Molecular and Cellular Biology.

[21]  X. D. Wang,et al.  Effects of physiological versus pharmacological beta-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets. , 2000, Carcinogenesis.

[22]  R. Davis,et al.  Signal Transduction by the JNK Group of MAP Kinases , 2000, Cell.

[23]  H. Rasmussen,et al.  The Effects of a Multivitamin/Mineral Supplement on Micronutrient Status, Antioxidant Capacity and Cytokine Production in Healthy Older Adults Consuming a Fortified Diet , 2000, Journal of the American College of Nutrition.

[24]  Z. Dong,et al.  ERKs and p38 Kinase Phosphorylate p53 Protein at Serine 15 in Response to UV Radiation* , 2000, The Journal of Biological Chemistry.

[25]  R. Flavell,et al.  The JNK and P38 MAP kinase signaling pathways in T cell-mediated immune responses. , 2000, Free radical biology & medicine.

[26]  V. Adler,et al.  p53 phosphorylation and association with murine double minute 2, c-Jun NH2-terminal kinase, p14ARF, and p300/CBP during the cell cycle and after exposure to ultraviolet irradiation. , 2000, Cancer research.

[27]  W. Hong,et al.  All-trans-Retinoic Acid Inhibits Jun N-Terminal Kinase by Increasing Dual-Specificity Phosphatase Activity , 1999, Molecular and Cellular Biology.

[28]  M. Russell,et al.  Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke. , 1999, Journal of the National Cancer Institute.

[29]  T. G. Truscott,et al.  β‐Carotene with vitamins E and C offers synergistic cell protection against NOx , 1998, FEBS letters.

[30]  W. Lei,et al.  Induction of apoptosis and activation of interleukin 1beta-converting enzyme/Ced-3 protease (caspase-3) and c-Jun NH2-terminal kinase 1 by benzo(a)pyrene. , 1998, Cancer research.

[31]  D. Meek,et al.  Multisite phosphorylation and the integration of stress signals at p53. , 1998, Cellular signalling.

[32]  Y Taya,et al.  DNA damage induces phosphorylation of the amino terminus of p53. , 1997, Genes & development.

[33]  Yoichi Taya,et al.  DNA Damage-Induced Phosphorylation of p53 Alleviates Inhibition by MDM2 , 1997, Cell.

[34]  M. Karin,et al.  Regulation and function of the JNK subgroup of MAP kinases. , 1997, Biochimica et biophysica acta.

[35]  P. Taylor,et al.  Intake of vitamins E, C, and A and risk of lung cancer. The NHANES I epidemiologic followup study. First National Health and Nutrition Examination Survey. , 1997, American journal of epidemiology.

[36]  J. Blumberg,et al.  Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. , 1997, JAMA.

[37]  E. Zandi,et al.  AP-1 function and regulation. , 1997, Current opinion in cell biology.

[38]  A. Weitberg,et al.  Effect of vitamin E and beta-carotene on DNA strand breakage induced by tobacco-specific nitrosamines and stimulated human phagocytes. , 1997, Journal of experimental & clinical cancer research : CR.

[39]  P. Stork,et al.  Mitogen-activated Protein Kinase Phosphatases Inactivate Stress-activated Protein Kinase Pathways in Vivo* , 1997, The Journal of Biological Chemistry.

[40]  E. Land,et al.  Carotenoids Enhance Vitamin E Antioxidant Efficiency , 1997 .

[41]  S. Mayne,et al.  Beta-Carotene and lung cancer promotion in heavy smokers--a plausible relationship? , 1996, Journal of the National Cancer Institute.

[42]  M R Cullen,et al.  Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. , 1996, Journal of the National Cancer Institute.

[43]  X. D. Wang,et al.  β-Oxidation in Rabbit Liver in Vitro and in the Perfused Ferret Liver Contributes to Retinoic Acid Biosynthesis from β-Apocarotenoic Acids* , 1996, The Journal of Biological Chemistry.

[44]  R. Davis,et al.  Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways , 1996, Journal of Molecular Medicine.

[45]  K. Kondo,et al.  A dose‐response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients , 1996, Journal of surgical oncology.

[46]  K. Yeum,et al.  Measurement of carotenoids, retinoids, and tocopherols in human lenses. , 1995, Investigative ophthalmology & visual science.

[47]  V. V. van Hinsbergh,et al.  Supplementation with low doses of vitamin E protects LDL from lipid peroxidation in men and women. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[48]  I. Jialal,et al.  The Effect of α-Tocopherol Supplementation on LDL Oxidation: A Dose-Response Study , 1995 .

[49]  John Calvin Reed,et al.  Tumor suppressor p53 is a direct transcriptional activator of the human bax gene , 1995, Cell.

[50]  A. C. Chan.  Partners in defense, vitamin E and vitamin C. , 1993, Canadian journal of physiology and pharmacology.

[51]  M. Gosney,et al.  Exposure to Cigarette Smoke and Expression of the Protein Encoded by the p53 Gene in Bronchial Carcinoma , 1993, Annals of the New York Academy of Sciences.

[52]  G. Schectman,et al.  Estimating Ascorbic Acid Requirements for Cigarette Smokers , 1993, Annals of the New York Academy of Sciences.

[53]  X. D. Wang,et al.  Intestinal perfusion of beta-carotene in the ferret raises retinoic acid level in portal blood. , 1993, Biochimica et biophysica acta.

[54]  X. D. Wang,et al.  Intestinal uptake and lymphatic absorption of beta-carotene in ferrets: a model for human beta-carotene metabolism. , 1992, The American journal of physiology.

[55]  M. Karin,et al.  Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73 , 1991, Nature.

[56]  H Tunstall-Pedoe,et al.  Antioxidant vitamin intakes assessed using a food-frequency questionnaire: correlation with biochemical status in smokers and non-smokers , 1991, British Journal of Nutrition.

[57]  R. Russell,et al.  Enzymatic conversion of β-carotene into β-apo-carotenals and retinoids by human, monkey, ferret, and rat tissues , 1991 .

[58]  H. Gruchow,et al.  The influence of smoking on vitamin C status in adults. , 1989, American journal of public health.

[59]  B. Ames,et al.  Antioxidant defenses and lipid peroxidation in human blood plasma. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[60]  R. Russell,et al.  Exposing ferrets to cigarette smoke and a pharmacological dose of beta-carotene supplementation enhance in vitro retinoic acid catabolism in lungs via induction of cytochrome P450 enzymes. , 2003, The Journal of nutrition.

[61]  D. Dungworth.  Histological classification of tumors of the respiratory system of domestic animals , 1999 .

[62]  W. Pryor,et al.  Beta carotene and its oxidation products have different effects on microsome mediated binding of benzo[a]pyrene to DNA. , 1999, Free radical biology & medicine.

[63]  H S Black,et al.  Radical interception by carotenoids and effects on UV carcinogenesis. , 1998, Nutrition and cancer.

[64]  D. Hoffmann,et al.  A study of tobacco carcinogenesis, LIII: carcinogenicity of N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mink (Mustela vison). , 1997, Cancer letters.

[65]  D. Albanes,et al.  The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. , 1994, The New England journal of medicine.

[66]  S. Lippman,et al.  Retinoid chemoprevention of upper aerodigestive tract carcinogenesis. , 1992, Important advances in oncology.

[67]  J. Erdman,et al.  β-Carotene Uptake and Tissue Distribution in Ferrets (Mustela putorius furo) , 1992 .