Skip to main content

Metabolism of Ethanol to Acetaldehyde in the Rat Mammary Tissue: Inhibitory Effects of Plant Polyphenols and Folic Acid

  • Chapter
  • First Online:
Alcohol, Nutrition, and Health Consequences

Abstract

Alcohol consumption is causally related to an increased risk of cancer of the upper aero-digestive tract, liver, colorectum, and female breast [1–5].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Stewart BW, Kleihues P. WHO – International Agency for Research on Cancer. World cancer report. Lyon: IARC Press; 2003. p. 29–32.

    Google Scholar 

  2. Baan R, Straif K, Grosse Y, et al. WHO International Agency for Research on Cancer monograph working group. Carcinogenicity of alcoholic beverages. Lancet Oncol. 2007;8:292–3.

    Article  PubMed  Google Scholar 

  3. Seitz HK, Stickel F. Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer. 2007;7:599–612.

    Article  PubMed  CAS  Google Scholar 

  4. Allen NE, Beral V, Casabonne D, et al. Million women study collaborators moderate alcohol intake and cancer incidence in women. J Natl Cancer Inst. 2009;101:296–305.

    Article  PubMed  Google Scholar 

  5. World Health Organization. IARC monographs on the evaluation of carcinogenic risk to humans, Alcohol consumption and ethyl carbamate, vol. 96. Lyon: IARC; 2010.

    Google Scholar 

  6. Hamajima N, Hirose K, Tajima K, et al. Collaborative group on hormonal factors in breast cancer. Alcohol, tobacco and breast cancer-collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer. 2002;87:1234–45.

    Article  PubMed  Google Scholar 

  7. Schütze M, Boeing H, Pischon T, et al. Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study. BMJ. 2011;342:d1584.

    Article  PubMed  Google Scholar 

  8. Garro AJ, Lieber CS. Alcohol and cancer. Annu Rev Pharmacol Toxicol. 1990;30:219–49.

    Article  PubMed  CAS  Google Scholar 

  9. Gavaler JS. Alcohol effects on hormone levels in normal postmenopausal women and in postmenopausal women with alcohol-induced cirrhosis. Recent Dev Alcohol. 1995;12:199–208.

    Article  PubMed  CAS  Google Scholar 

  10. Ginsburg ES. Estrogen, alcohol and breast cancer risk. J Steroid Biochem Mol Biol. 1999;69:299–306.

    Article  PubMed  CAS  Google Scholar 

  11. Singletary KW, Gapstur SM. Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms. JAMA. 2001;286:2143–51.

    Article  PubMed  CAS  Google Scholar 

  12. Dumitrescu RG, Shields PG. The etiology of alcohol-induced breast cancer. Alcohol. 2005;35:213–25.

    Article  PubMed  CAS  Google Scholar 

  13. Przylipiak A, Rabe T, Hafner J, et al. Influence of ethanol on in vitro growth of human mammary carcinoma cell line MCF-7. Arch Gynecol Obstet. 1996;258:137–40.

    Article  PubMed  CAS  Google Scholar 

  14. Singletary KW, Frey RS, Yan W. Effect of ethanol on proliferation and estrogen receptor-alpha expression in human breast cancer cells. Cancer Lett. 2001;165:131–7.

    Article  PubMed  CAS  Google Scholar 

  15. Izevbigie EB, Ekunwe SI, Jordan J, et al. Ethanol modulates the growth of human breast cancer cells in vitro. Exp Biol Med (Maywood). 2002;227:260–5.

    CAS  Google Scholar 

  16. Coutelle C, Höhn B, Benesova M, et al. Risk factors in alcohol associated breast cancer: alcohol dehydrogenase polymorphism and estrogens. Int J Oncol. 2004;25:1127–32.

    PubMed  CAS  Google Scholar 

  17. Etique N, Chardard D, Chesnel A, et al. Ethanol stimulates proliferation, ERalpha and aromatase expression in MCF-7 human breast cancer cells. Int J Mol Med. 2004;13:149–55.

    PubMed  CAS  Google Scholar 

  18. Izevbigie EB. Signaling pathways in human breast cells in response to alcohol: mechanisms for alcohol-induced breast cancer. In: Watson RR, Preedy V, editors. Comprehensive handbook of alcohol-related pathology, vol. 2. London: Elsevier Science/Academic; 2005. p. 1017–25.

    Chapter  Google Scholar 

  19. Purohit V. Moderate alcohol consumption and estrogen levels in postmenopausal women: a review. Alcohol Clin Exp Res. 1998;22:994–7.

    Article  PubMed  CAS  Google Scholar 

  20. Li CI, Malone KE, Porter PL, Weiss NS, Tang MT, Daling JR. The relationship between alcohol use and risk of breast cancer by histology and hormone receptor status among women 65–79 years of age. Cancer Epidemiol Biomarkers Prev. 2003;12:1061–6.

    PubMed  CAS  Google Scholar 

  21. Cavalieri EL, Rogan EG. Depurinating estrogen-DNA adducts in the etiology and prevention of breast and other human cancers. Future Oncol. 2010;6:75–91.

    Article  PubMed  CAS  Google Scholar 

  22. Castro GD, de Castro CR, Maciel ME, et al. Ethanol-induced oxidative stress and acetaldehyde formation in rat mammary tissue: potential factors involved in alcohol drinking promotion of breast cancer. Toxicology. 2006;219:208–19.

    Article  PubMed  CAS  Google Scholar 

  23. Fanelli SL, Maciel ME, Díaz Gómez MI, et al. Further studies on the potential contribution of acetaldehyde accumulation and oxidative stress in rat mammary tissue in the alcohol drinking promotion of breast cancer. J Appl Toxicol. 2011;1:11–9.

    Article  Google Scholar 

  24. Freudenheim JL, Ambrosone CB, Moysich KB, et al. Alcohol dehydrogenase 3 genotype modification of the association of alcohol consumption with breast cancer risk. Cancer Causes Control. 1999;10:369–77.

    Article  PubMed  CAS  Google Scholar 

  25. Zheng T, Holford TR, Zahm SH, et al. Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk. Br J Cancer. 2003;88:58–62.

    Article  PubMed  CAS  Google Scholar 

  26. Castro GD, Delgado de Layño AM, Fanelli SL, et al. Acetaldehyde accumulation in rat mammary tissue after an acute treatment with alcohol. J Appl Toxicol. 2008;28:315–21.

    Article  PubMed  CAS  Google Scholar 

  27. Castro GD, Delgado de Layño AM, Costantini MH, et al. Cytosolic xanthine oxidoreductase mediated bioactivation of ethanol to acetaldehyde and free radicals in rat breast tissue. Its potential role in alcohol-promoted ­mammary cancer. Toxicology. 2001;160:11–8.

    Article  PubMed  CAS  Google Scholar 

  28. Fam AG. Gout: excess calories, purines, and alcohol intake and beyond. Response to a urate-lowering diet. J Rheumatol. 2005;32:773–7.

    PubMed  CAS  Google Scholar 

  29. Jarasch ED, Grund C, Brunder G, et al. Localization of xanthine oxidase in mammary gland epithelium and capillary endothelium. Cell. 1981;25:67–82.

    Article  PubMed  CAS  Google Scholar 

  30. Kooij A, Frederiks WM, Gossrau R, et al. Localization of xanthine oxidoreductase activity using the tissue protectant polyvinyl alcohol and final electron acceptor Tetranitro BT. J Histochem Cytochem. 1991;39:87–93.

    Article  PubMed  CAS  Google Scholar 

  31. Bartel LC, Montalto de Mecca M, Castro JA. Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions. Food Chem Toxicol. 2009;47:140–4.

    Article  PubMed  CAS  Google Scholar 

  32. Maciel ME, Castro GD, Castro JA. Inhibition of the rat breast cytosolic bioactivation of ethanol to acetaldehyde by some plant polyphenols and folic acid. Nutr Cancer. 2004;49:94–9.

    Article  PubMed  CAS  Google Scholar 

  33. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA. 1999;281:1632–7.

    Article  PubMed  CAS  Google Scholar 

  34. Rohan TE, Jain M, Miller AB. Alcohol consumption and risk of benign proliferative epithelial disorders of the breast: a case-cohort study. Public Health Nutr. 1998;1:139–45.

    Article  PubMed  CAS  Google Scholar 

  35. Sellers TA, Vierkant RA, Cerhan JR, et al. Interaction of dietary folate intake, alcohol, and risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2002;11:1104–7.

    PubMed  CAS  Google Scholar 

  36. Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology. 2001;12:420–8.

    Article  PubMed  CAS  Google Scholar 

  37. Lucock M. Folic acid: nutritional biochemistry, molecular biology and role in disease processes. Mol Genet Metab. 2000;71:121–38.

    Article  PubMed  CAS  Google Scholar 

  38. Hamid A, Wani NA, Kaur J. New perspectives on folate transport in relation to alcoholism-induced folate malabsorption. Association with epigenome stability and cancer development. FEBS J. 2009;276:2175–91.

    Article  PubMed  CAS  Google Scholar 

  39. Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr. 2003;78:559S–69.

    PubMed  CAS  Google Scholar 

  40. Temple NJ, Gladwin KK. Fruit, vegetables and the prevention of cancer: research challenges. Nutrition. 2003;19:467–70.

    Article  PubMed  Google Scholar 

  41. Yang CS, Maliakal P, Meng X. Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol. 2002;42:25–54.

    Article  PubMed  CAS  Google Scholar 

  42. Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem. 2002;13:572–4.

    Article  PubMed  CAS  Google Scholar 

  43. Yang CS, Prabhu S, Landau J. Prevention of carcinogenesis by tea polyphenols. Drug Metab Rev. 2001;33:237–53.

    Article  PubMed  CAS  Google Scholar 

  44. Moran TF, Klucas RV, Grayer RJ, et al. Complexes of iron with phenolic compounds from soybean nodules and other legume tissues: prooxidant and antioxidant properties. Free Radic Biol Med. 1997;22:861–70.

    Article  PubMed  CAS  Google Scholar 

  45. Guerri C, Sanchis R. Alcohol and acetaldehyde in rat’s milk following ethanol administration. Life Sci. 1986;28:1543–56.

    Article  Google Scholar 

  46. Triano EA, Slusher LB, Atkins TA, et al. Class I alcohol dehydrogenase is highly expressed in normal human mammary epithelium but not in invasive breast cancer: implications for breast carcinogenesis. Cancer Res. 2003;63:3092–100.

    PubMed  CAS  Google Scholar 

  47. Castro GD, Delgado de Layño AM, Costantini MH, et al. Rat breast microsomal biotransformation of ethanol to acetaldehyde but not to free radicals: its potential role in the association between alcohol drinking and breast tumor promotion. Teratog Carcinog Mutagen. 2003;23 Suppl 1:61–70.

    Article  Google Scholar 

  48. Leclercq I, Horsmans Y, Desager J. Estimation of chlorzoxazone hydroxylase activity in liver microsomes and of the plasma pharmacokinetics of chlorzoxazone by the same high-performance liquid chromatographic method. J Chromatogr A. 1998;828:291–6.

    Article  PubMed  CAS  Google Scholar 

  49. Díaz Gómez MI, Fanelli SL, Delgado de Layño AMA, et al. Deleterious effects induced by oxidative stress in liver nuclei from rats receiving an alcohol containing liquid diet. Toxicol Ind Health. 2008;24:625–34.

    Article  PubMed  Google Scholar 

  50. O’Brien PJ. Peroxidases. Chem Biol Interact. 2000;129:113–39.

    Article  PubMed  Google Scholar 

  51. Natarajan R, Nadler J. Role of lipoxygenases in breast cancer. Front Biosci. 1998;3:E81–8.

    PubMed  CAS  Google Scholar 

  52. Kulkarni AP, Cai Y, Richards IS. Rat pulmonary lipoxygenase: dioxygenase activity and role in xenobiotic metabolism. Int J Biochem. 1992;24:255–61.

    Article  PubMed  CAS  Google Scholar 

  53. Pinto MC, García-Barrado JA, Macías P. Resveratrol is a potent inhibitor of the dioxygenase activity of lipoxygenase. J Agric Food Chem. 1999;47:4842–6.

    Article  PubMed  CAS  Google Scholar 

  54. Hover CG, Kulkarni AP. Hydroperoxide specificity of plant and human tissue lipoxygenase: an in vitro evaluation using N-demethylation of phenothiazines. Biochim Biophys Acta. 2000;1475:256–64.

    Article  PubMed  CAS  Google Scholar 

  55. Pinto Mdel C, Macias P. Oxidation of dietary polyphenolics by hydroperoxidase activity of lipoxygenase. J Agric Food Chem. 2005;53:9225–30.

    Article  PubMed  Google Scholar 

  56. Doussiere J, Gaillard J, Vignais PV. The heme component of the neutrophil NADPH oxidase complex is a target for aryliodonium compounds. Biochemistry. 1999;38:3694–703.

    Article  PubMed  CAS  Google Scholar 

  57. Lieber CS. Alcohol metabolism: general aspects. In: Watson RR, Preedy V, editors. Comprehensive handbook of alcohol related pathology, vol. 1. London: Elsevier Science/Academic; 2005. p. 1211–22.

    Google Scholar 

  58. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30:1–12.

    Article  PubMed  CAS  Google Scholar 

  59. Blatt DH, Prior WA, Mata JE, et al. Re-evaluation of the relative potency of synthetic and natural alpha-tocopherol: experimental and clinical observations. J Nutr Biochem. 2004;15:380–95.

    Article  PubMed  CAS  Google Scholar 

  60. Woutersen RA, Appelman LM, Feron VJ, Van der Heijden CA. Inhalation toxicity of acetaldehyde in rats. II. Carcinogenicity study: interim results after 15 months. Toxicology. 1984;31:123–33.

    Article  PubMed  CAS  Google Scholar 

  61. Woutersen RA, Appelman LM, Van Garderen-Hoetmer A, Feron VJ. Inhalation toxicity of acetaldehyde in rats. III. Carcinogenicity study. Toxicology. 1986;41:213–31.

    Article  PubMed  CAS  Google Scholar 

  62. Dellarco VL. A mutagenicity assessment of acetaldehyde. Mutat Res. 1988;195:1–20.

    Article  PubMed  CAS  Google Scholar 

  63. Petersen DR. Alcohol, iron-associated oxidative stress, and cancer. Alcohol. 2005;35:243–9.

    Article  PubMed  CAS  Google Scholar 

  64. Halliwell B. Oxidative stress and cancer: have we moved forward? Biochem J. 2007;401:1–11.

    Article  PubMed  CAS  Google Scholar 

  65. Salaspuro V. Pharmacological treatments and strategies for reducing oral and intestinal acetaldehyde. Novartis Found Symp. 2007;285:145–53.

    Article  PubMed  CAS  Google Scholar 

  66. Salaspuro M. Acetaldehyde and gastric cancer. J Dig Dis. 2011;12:51–9.

    Article  PubMed  CAS  Google Scholar 

  67. Maciel ME, Castro JA, Castro GD. Inhibition of rat mammary microsomal oxidation of ethanol to acetaldehyde by plant polyphenols. Hum Exp Toxicol. 2011;30:656–64.

    Article  PubMed  CAS  Google Scholar 

  68. Collins-Burow BM, Burow ME, Duong BN, et al. Estrogenic and antiestrogenic activities of flavonoid phytochemicals through estrogen receptor binding-dependent and -independent mechanisms. Nutr Cancer. 2000;38:229–44.

    Article  PubMed  CAS  Google Scholar 

  69. Kim S, Lee MJ, Hong J, et al. Plasma and tissue levels of tea catechins in rats and mice during chronic consumption of green tea polyphenols. Nutr Cancer. 2000;37:41–8.

    Article  PubMed  CAS  Google Scholar 

  70. Rasmussen SE, Miller Breinholt V. Non-nutritive bioactive food constituents of plants: bioavailability of flavonoids. Int J Vitam Nutr Res. 2003;73:101–11.

    Article  PubMed  CAS  Google Scholar 

  71. Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phytoestrogens in Japanese men and women consuming a traditional Japanese diet. Am J Clin Nutr. 1993;342:1209–10.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José Alberto Castro Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Castro, G.D., Castro, J.A. (2013). Metabolism of Ethanol to Acetaldehyde in the Rat Mammary Tissue: Inhibitory Effects of Plant Polyphenols and Folic Acid. In: Watson, R., Preedy, V., Zibadi, S. (eds) Alcohol, Nutrition, and Health Consequences. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-047-2_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-047-2_12

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-046-5

  • Online ISBN: 978-1-62703-047-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics