Acetaldehyde, microbes, and cancer of the digestive tract

Critical Reviews in Clinical Laboratory Sciences

Volumn 40, Issue 2, 2003, Pages 183-208

  Salaspuro, Mikko P ^a   Mezey, Esteban ^b  

^a HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Acetaldehyde; Alcohol; Alcohol dehydrogenase; Aldehyde dehydrogenase; Atrophic gastritis; Bacteria; Cancer; Colon cancer; Digestive tract; Esophageal cancer; Ethanol; Gastric cancer; Gut flora; Helicobacter pylori; Microbes; Oral cancer

Indexed keywords

ACETALDEHYDE; ALCOHOL; ALCOHOL DEHYDROGENASE; ALDEHYDE DEHYDROGENASE;

ACHLORHYDRIA; ALCOHOL CONSUMPTION; ALCOHOL OXIDATION; ATROPHIC GASTRITIS; BACTERIAL INFECTION; BACTERIAL OVERGROWTH; CANCER RISK; COLON CANCER; CONTROLLED STUDY; DIGESTIVE SYSTEM CANCER; ENZYME DEFICIENCY; FERMENTATION; GASTRITIS; HELICOBACTER PYLORI; HUMAN; INTESTINE FLORA; MOUTH CANCER; NONHUMAN; PRIORITY JOURNAL; REVIEW; STOMACH CANCER;

ANIMALIA; BACTERIA (MICROORGANISMS); HELICOBACTER; HELICOBACTER PYLORI;

EID: 0037623310     PISSN: 10408363     EISSN: None     Source Type: Journal    
DOI: 10.1080/713609333     Document Type: Review

References (147)

1. Doll R, Forman D, La Vecchia C, et al. Alcoholic beverages and cancers of the digestive tract and larynx. In: MacDonald I, ed. Health Issues Related to Alcohol Consumption. Pp. 351-93. Bodmin, Cornwall: MPG Books 1999.
2. IARC. Alcohol drinking. In: IARC monographs on the evaluation of the carcinogenic risk to humans. Vol. 44, Pp. 1-416. Lyon: International Agency for Research on Cancer, 1988.
3. Seitz HK, Simanowski UA. Alcohol and carcinogenesis. Annu Rev Nutr 1988; 8: 99-119.
4. Seitz HK, Pöschl G, Simanowski UA. Alcohol and cancer. In: Galanter M, ed. Recent developments in alcoholism. Vol. 14, Pp. 67-95. New York: Plenum Press, 1998.
5. Homann N. Alcohol and upper gastrointestinal tract cancer: the role of local acetaldehyde production. Addict Biology 2001; 6: 309-23.
6. IARC. Acetaldehyde. In: IARC monographs on the evaluation of the carcinogenic risk to humans. Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. Vol. 71, Pp. 319-35. Lyon: International Agency for Research on Cancer, 1999.
7. Lieber CS. Microsomal ethanol oxidizing system (MEOS): The first 30 years (1968-1998) - a review. Alcohol Clin Exp Res 1999; 23: 991-1007.
8. Halsted CH, Robles SA Mezey E. Distribution of ethanol in the human gastrointestinal tract. Am J Clin Nutr 1973; 26: 831-4.
9. Jones AW. Distribution of ethanol between saliva and blood in man. Clin Exp Pharmacol Physiol 1979; 6: 53-9.
10. Jokelainen K, Matysiak-Budnik T, Mäkisalo H, et al. High intracolonic acetaldehyde values produced by a bacteriocolonic pathway for ethanol oxidation in piglets. Gut 1996; 39: 100-4.
11. Wynder EL, Covey LS, Mabuchi K, et al. Environmental Factors in cancer of the larynx: a second look. Cancer 1976; 38: 1591-601.
12. Pottern LM, Morris LE, Blot WJ, et al. Esophageal cancer among black men in Washington DC. I. Alcohol, tobacco, and other risk factors. J Natl Cancer Inst 1981; 67: 777-83.
13. Tuyns AG. Oesophageal cancer in non-smoking drinkers and in non drinking smokers. Int J Cancer 1983; 32: 443-4.
14. Elwood JM, Pearson JCG, Skippen DH, et al. Alcohol, smoking, social and occupational factors in the aetiology of cancer of the oral cavity, pharynx and larynx. Int J Cancer 1984; 34: 603-12.
15. Brugere J, Guenel P, Leclerc A, et al. Differential effects of tobacco and alcohol in cancer of the larynx, pharynx and mouth. Cancer 1986; 57: 391-5.
16. Tuyns AJ, Esteve J, Berrino F, et al. Cancer of the larynx/hypopharynx, tobacco and alcohol. Int J Cancer 1988; 41: 483-91.
17. Tavani A, Negri E, Franceschi S, et al. Risk factors for oesophageal cancer in lifelong nonsmokers. Cancer Epidemiol Biomarkers Prev 1994; 3: 387-92.
18. Ng SKC, Kabat GC, Wynder EL. Oral cavity cancer in non-users of tobacco. J Natl Cancer Inst 1993; 85: 743-5.
19. Maier H, Zöller J, Herrmann A, et al. Dental status and oral hygiene in patients with head and neck cancer. Otolaryngol Head Neck Surg 1993; 1088: 655-61.
20. Ziegler RG. Alcohol-nutrient interactions in cancer etiology. Cancer 1986; 58: 1942-8.
21. Correa P, Fontham E, Pickle WL, et al. Dietary determinants of gastric cancer in south Louisiana inhabitants. J Natl Cancer Inst 1985; 75: 645-54.
22. Hoye J, Montvernay C, Lambert R. Wine and tobacco: risk factors for gastric cancer in France. Am J Epidemiol 1981; 113: 668-74.
23. Wang HH, Antonioli DA, Goldman H. Comparative feature of esophageal and gastric adenocarcinomas: recent changes in type and frequency. Hum Pathol 1986; 17: 482-7.
24. Graham S, Lilienfeld AM, Tidings JE. Dietary and purgation factors in the epidemiology of gastric cancer. Cancer 1967; 20: 2224-34.
25. Graham S, Schotz W, Martino P. Alimentary factors in the epidemiology of gastric cancer. Cancer 1972; 30: 927-38.
26. Gray JR, Goldman AJ, MacDonald WC. Cigarette and alcohol use in patients with adenocarcinoma of the gastric cardia or lower esophagus. Cancer 1992; 69: 2227-31.
27. Kato I, Tominaga S, Matsumoto K. A prospective study of stomach cancer among a rural Japanese population: a 6-year survey. Jpn J Cancer Res 1992; 83: 568-575.
28. Yokoyama A, Muramatsu T, Ohmori T, el al. Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics. Carcinogenesis 1998; 19: 1383-7.
29. Goedde HW, Harada S, Agarwall DP. Racial differences in alcohol sensitivity: a new hypothesis. Hum Genet 1979; 51: 331-4.
30. Kune GA, Vitetta L. Alcohol consumption and the etiology of colorectal cancer: a review of the scientific evidence from 1957 to 1991. Nutr Cancer 1992; 18: 97-111.
31. Longnecker MP, Orza MJ, Adams ME, et al. A meta-analysis of alcoholic beverage consumption in relation to risk of colorectal cancer. Cancer Causes Control 1990; 1: 59-68.
32. Scheppach W, Bingham S, Boutron-Rualt M-C, et al. WHO Consensus statement on the role of nutrition in colorectal cancer. Eur J Cancer Prev 1999; 8: 57-62.
33. Agarwall DP. Molecular genetic aspects of alcohol metabolism and alcoholism. Pharmacopsychiatry 1997; 30: 79-84.
34. Lands WEM. A review of alcohol clearance in humans. Alcohol 1998; 15: 147-60.
35. Crabb DW, Edenberg HJ, Bosron WF, et al. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2*2 allele is dominant. J Clin Invest 1989; 83: 314-6.
36. Goedde HW. Agarwal DP, Fritze G, et al. Distribution of ADH2 and ALDH2 genotypes in different populations. Hum Genet 1992; 88: 344-6.
37. Mizoi Y, Ijiri I, Tatsuno Y, et al. Relationship between facial flushing and blood acetaldehyde levels after alcohol intake. Pharmacol Biochem Behav 1979; 10: 303-11.
38. Eriksson CJ, Fukunaga T. Human blood acetaldehyde (update 1992). Alcohol Alcohol 1993; 2 (Suppl.): 9-25.
39. Harada S, Agarwal DP, Goedde HW. Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese. Lancet 1981; 2: 982.
40. Peng G-S, Wang M-F, Chen C-Y, et al. Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians. Pharmacogenetics 1999; 9: 463-76.
41. Chen C-C, Lu Ru, Chen Y-C, et al. Interaction between the functional polymorphism of the alcohol-metabolism genes in protection against alcoholism. Am J Hum Genet 1999; 65: 795-807.
42. Higuchi S, Matsushita S, Imazeki H, et al. Polymorphism of ethanol metabolising enzyme genes and alcoholism. Alcohol Alcohol 1994; 2(Suppl.): 29-34.
43. Yokoyama A, Muramatsu T, Ohmori T, et al. Esophageal cancer and aldehyde dehydrogenase-2 genotypes in Japanese males. Cancer Epidemiol Biomarkers Prev 1996; 5: 99-102.
44. Yokoyama A, Muramatsu T, Ohmori T, et al. Multiple primary esophageal and concurrent upper aerodigestive tract cancer and aldehyde dehydrogenase-2 genotype of Japanese alcoholics. Cancer 1996; 77: 1986-90.
45. Murata M, Tagawa M, Watanabe S, et al. Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients. Jpn J Cancer Res 1999; 90: 711-9.
46. Bosron WF, Li T-K. Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology 1986; 6: 502-10.
47. Coutelle C, Ward PJ, Fleury B, et al. Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathine S-transferase MI polymorphism. Hum Genet 1997; 99: 319-25.
48. Harry LC, Caporaso NE, Hayes RB, et al. Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal cancers. J Natl Cancer Inst 1997; 89: 1698-705.
49. Bouchardy C, Hirvonen A, Coutelle C, et al. Role of alcohol dehydrogenase 3 and cytochrome P-4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract. Int J Cancer 2000; 87: 734-40.
50. Olshan AF, Weissler MC, Watson MA, et al. Risk of head and neck cancer and the alcohol dehydrogenase 3 genotype. Carcinogenesis 2001; 22: 57-61.
51. Hori H, Kawano T, Endo M, et al. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and human esophageal squamous cell carcinoma susceptibility. J Clin Gastroenterol 1997; 25: 568-75.
52. Chao YC, Wang LS, Hsieh TY, et al. Chinese alcoholic patients with esophageal cancer are genetically different from alcoholics with acute pancreatitis and liver cirrhosis. Am J Gastroenterol 2000; 95: 2958-64.
53. Yokoyama A, Muramatsu T, Omori T, et al. Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics. Alcohol Clin Exp Res 1999; 23: 1705-10.
54. Reid MF, Fewson CA. Molecular characterization of microbial alcohol dehydrogenase. Crit Rev Microbiol 1994; 20: 13-56.
55. Zeikus JG. Chemical and fuel production by anaerobic bacteria. Anuu Rev Microbiol 1980; 34: 423-64.
56. Neale AD, Scopes RK, Kelly JM, et al. The two alcohol dehydrogenases of Zymomonas mobilis. Purification by differential dye ligand chromatography, molecular characterisation and physiological roles. Eur J Biochem 1986; 154: 119-124.
57. Krebs HA, Perkins JR. The physiological role of liver alcohol dehydrogenase. Biochem J 1970; 118: 635-44.
58. Baraona E, Julkunen R, Tannenbaum L, et al. Role of intestinal bacterial overgrowth in ethanol production and metabolism in rats. Gastroenterology 1986; 90: 103-10.
59. Klipstein FA, Holdeman LV, Corcino JJ, et al. Enterotoxigenic intestinal bacteria in tropical sprue. Ann Int Med 1973; 79: 632-41.
60. Mezey E, Imbembo AL, Potter JJ, et al. Endogenous ethanol production and hepatic disease following jejunoileal bypass for morbid obesity. Am J Clin Nut 1975; 28: 1277-83.
61. Bode JC, Rust S, Bode C. The effect of cimetidine treatment on ethanol formation in the human stomach. Scand J Gastroenterol 1984; 19: 853-6.
62. Kaji H, Asanuma Y, Yahara O, et al. Intragastrointestinal alcohol fermentation syndrome: Report of two cases and review of the literature. J Forensic Sci Soc 1984; 24: 461-71.
63. Miyakawa H, Baraona E, Chang JC, et al. Oxidation of ethanol to acetaldehyde by broncho-pulmonary washings: role of bacteria. Alcohol Clin Exp Res 1986; 10: 517-20.
64. Pikkarainen PH, Baraona E, Jauhonen P, et al. Contribution of oropharynx microflora and of lung microsomes to acetaldehyde in expired air after alcohol ingestion. J Lab Clin Med 1981; 97: 631-6.
65. Homann N, Jousimies-Somer H, Jokelainen K, et al. High acetaldehyde levels in saliva after ethanol consumption: Methodological aspects and pathogenetic implications. Carcinogenesis 1997; 18: 1739-43.
66. Stowell AR. An improved method for the determination of acetaldehyde in human blood with minimal ethanol interference. Clin Chim Acta 1979; 98: 201-5.
67. Homann N, Tillonen J, Meunnan J, et al. Increased salivary acetaldehyde levels in heavy drinkers and smokers: a microbiological approach to oral cavity cancer. Carcinogenesis 2000; 22: 663-8.
68. Homann N, Tillonen J, Rintamäki H, et al. Poor dental status increases the acetaldehyde production from ethanol in saliva: a possible link to the higher risk of oral cancer among alcohol consumers. Oral Oncol 2001; 37: 153-8.6
69. WHO report: Environmental health criteria 167: Acetaldehyde. Geneva: World Health Organization, 1995 Pp. 1-47.
70. Holmstrup P, Bessermann M. Clinical, therapeutic and pathogenteic aspects of oral multifocal candidiasis. Oral Surg Oral Med Oral Pathol 1983; 56: 388-95.
71. Colman G, Beighton D, Chalk AJ, et al. Cigarrette smoking and the microbial flora of the mouth. Aust Dent J 1976; 21: 111-8.
72. Harris CK, Warnakulasuriya KA, Johnson NW, et al. Oral health in alcohol misusers. Community Dent Health 1996; 13: 199-203.
73. Mater H, Born IA, Veith S, et al. The effect of chronic ethanol consumption on salivary gland morphology and function in the rat. Alcohol Clin Exp Res 1986; 10: 425-9.
74. Jokelainen K, Heikkonen E, Roine R, et al. Increased acetaldehyde production by mouthwashings from patients with oral cavity, laryngeal, or pharyngeal cancer. Alcohol Clin Exp Res 1996; 20: 1206-10.
75. Tillonen J, Homann N, Rautio M, et al. Role of yeasts in the salivary acetaldehyde production from ethanol among risk groups for ethanol-associated oral cavity cancer. Alcohol Clin Exp Res 1999; 23: 1409-15.
76. Muto M, Hitomi Y, Ohtsu A, et al. Acetaldehyde production by non-pathogenic Neisseria in human oral microflora: implications for carcinogenesis in upper aerodigestive tract. Int J Cancer 2000; 88: 342-50.
77. Steinman CR, Jakoby WB. Yeast aldehyde dehydrogenase. II. Properties of the homogeneous enzyme preparations. J Biol Chem 1968; 243: 730-4.
78. Burdette D, Zeikus JG. Purification of acetaldehyde dehydrogenase and alcohol dehydrogenases from Thermoanaerobacter ethanolicus 39E and characterization of the secondary-alcohol dehydrogenase (2° Adh) as a bifunctional alcohol dehydrogenase-acetyl-CoA reductive thioesterase. Biochem J 1994; 302: 163-70.
79. Nosova T, Jokelainen K, Kaihovaara P, et al. Aldehyde dehydrogenase activity and acetate production by aerobic bacteria representing the normal flora of human large intestine. Alcohol Alcohol 1996; 31: 555-64.
80. Nosova T, Jokelainen K, Kaihovaara P, et al. Characteristics of aldehyde dehydrogenases of certain aerobic bacteria representing human colonic flora. Alcohol Alcohol 1998; 33: 273-80.
81. Nosova T, Jousimies-Somer H, Jokelainen K, et al. Acetaldehyde production and metabolism by human indigenous and probiotic lactobacillus and bifidobacterium strains. Alcohol Alcohol 2000; 35: 561-8.
82. Osborne JP, de Orduna MR, Pilone GJ, et al. Acetaldehyde metabolism by wine lactic acid bacteria. FEMS Microbiol Lett 2000; 191: 561-5.
83. Marshall BJ. Helicobacter pylori. Am J Gastroenterol 1994; 89: S116-28.
84. NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. J Am Med Assoc 1994; 272: 65-9.
85. Roine RP, Salmela KS, Höök-Nikanne J, et al. Alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori - a possible mechanism behind gastric injury. Life Sci 1992; 51: 1333-7.
86. Salmela KS, Roine RP, Koivisto T, et al. Characteristics of Helicobacter pylori alcohol dehydrogenase. Gastroenterology 1993; 105: 325-30.
87. Kaihovaara P, Salmela KS, Roine RP, et al. Purification and characterization of Helicobacter pylori alcohol dehydrogenase. Alcohol Clin Exp Res 1994; 18: 1220-5.
88. Roine RP, Salmela KS, Höök-Nikanne J, et al. Colloidal bismuth subcitrate and omeprazole inhibit alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori. Life Sci 1992; 51: PL195-200.
89. Salmela KS, Roine RP, Höök-Nikanne J, et al. Effect of bismuth and nitecapone on acetaldehyde production by Helicobacter pylori. Scand J Gastroenterol 1994; 29: 528-31.
90. Sahnela KS, Roine RP, Höök-Nikanne J, et al. Acetaldehyde and ethanol production by Helicobacter pylori. Scand J Gastroenterol 1994; 29: 309-12.
91. Stockbruegger RW, Cotton PB, Menon GG, et al. Pernicious anaemia, intragastric bacterial overgrowth and possible consequences. Scand J Gastroenterol 1984; 19: 355-64.
92. Stockbruegger RW. Bacterial overgrowth as a consequence of reduced gastric acidity. Scand J Gastroenterol 1985; 20(Suppl. 111): 7-15.
93. Fried M, Siegrist H, Frei R, et al. Duodenal bacterial overgrowth during treatment in outpatients with omeprazole. Gut 1994; 35: 23-6.
94. Verdu E, Viani F, Armstrong D et al. Effect of omeprazole on intragastric bacterial counts, nitrates, nitrites, and N-nitroso-compounds. Gut 1980; 35: 455-60.
95. Ruddell WSJ, Axon ATR, Findlay JM, et al. Effect of cimetidine on the gastric bacterial flora Lancet 1980; 29: 672-4.
96. 2-receptor antagonists. Digestion 1983; 28: 158-63.
97. Thorens J, Froehlich F, Schwizer W, et al. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomized double blind study. Gut 1996; 39: 54-9.
98. Drasar BS, Shiner M, McLeod. Studies on the intestinal flora I. The bacterial flora of the gastrointestinal tract in healthy and achlorhydric persons. Gastroenterology 1969; 56: 71-9.
99. Väkeväinen S, Tillonen J, Salaspuro M, et al. Hypochlorhydria induced by a proton pump inhibitor leads to intragastric microbial production of acetaldehyde from ethanol. Aliment Pharmacol Ther 2000; 14: 1511-8.
100. Väkeväinen S, Mentula S, Nuutinen H, et al. Ethanol-derived microbial production of carcinogenic acetaldehyde in achlorhydric atrophic gastritis. Scand J Gastroenterol 2002; 37: 648-55.
101. Morson BC, Sobin LH, Grundman E, et al. Precancerous conditions and epithelial dysplasia in the stomach. J Clin Pathol 1980; 33: 711-21.
102. Luckey TD. Bicentennial overview of intestinal microecology. Am J Clin Nutr 1977; 30: 1753-61.
103. Savage DC. Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 1977; 31: 107-33.
104. Bingham SA. Meat, starch, and nonstarch polysaccharides and large bowel cancer. Am J Clin Nutr 1988; 48: 762-7.
105. Cummings JH. Fermentation in the human large intestine: evidence and implications for health. Lancet 1983; I: 1206-9.
106. Banwell JG, Branch WJ, Cummings JH. The microbial mass in the human large intestine. Gastroenterology 1981; 80: 1104.
107. Macfarlane GT, Macfarlane S. Human colonic microbiota: Ecology, physiology and metabolic potential of intestinal bacteria. Scand J Gastroenterol 1997; 32(Suppl.): 3-9.
108. Stephen AM, Cummings JH. The microbial contribution to human faecal mass. J Med Microbiol 1980; 13: 45-56.
109. Still JL. Alcohol enzyme of Bact. coli. Biochem J 1940; 34: 1177-82.
110. Jokelainen K, Siitonen A, Jousimies-Somer H, et al. In vitro alcohol dehydrogenase-mediated acetaldehyde production by aerobic bacteria representing the normal colonic flora in man. Alcohol Clin Exp Res 1996; 20: 967-72.
111. Nosova T, Jousimies-Somer H, Kaihovaara P, et al. Characteristics of alcohol dehydrogenases of certain aerobic bacteria representing human colonic flora. Alcohol Clin Exp Res 1997; 21: 489-94.
112. Matysiak-Budnik T, Jokelainen K, Kärkkäinen P, et al. Hepatotoxicity and absorption of extrahepatic acetaldehyde in rats. J Pathol 1996; 178: 469-74.
113. Seitz HK, Simanowski UA, Garzon FT, et al. Possible role of acetaldehyde in ethanol-related rectal cocarcinogenesis in the rat. Gastroenterology 1990; 98: 406-13.
114. Salaspuro V, Nyfors S, Heine R, et al. Ethanol oxidation and acetaldehyde production in vitro by human intestinal strains of Escherichia coli under aerobic, microaerobic and anaerobic conditions. Scand J Gastroenterol 1999; 34: 967-73.
115. Jokelainen K, Roine RP, Väänänen H, et al. In vitro acetaldehyde formation by human colonic bacteria. Gut 1994; 35: 1271-4.
116. Tillonen J, Kaihovaara P, Jousimies-Somer H, et al. Role of catalase in in vitro acetaldehyde formation by human colonic contents. Alcohol Clin Exp Res 1998; 22: 1113-9.
117. Yin S-J, Liao C-S, Lee Y-C, et al. Genetic polymorphism and activities of human colon alcohol and aldehyde dehydrogenases: No gender and age differences. Alcohol Clin Exp Res 1994; 18: 1256-60.
118. Koivisto T, Salaspuro M. Aldehyde dehydrogenases of rat colon: Comparison with other tissues of the alimentary tract and the liver. Alcohol Clin Exp Res 1996; 20: 551-5.
119. Jokelainen K, Nosova T, Koivisto T, et al. Inhibition of bacteriocolonic pathway for ethanol oxidation by ciprofloxacin in rats. Life Sci 1997; 61: 1755-62.
120. Visapää J-P, Jokelainen K, Nosova T, et al. Inhibition of intracolonic acetaldehyde production and alcoholic fermentation in rats by ciprofloxacin. Alcohol Clin Exp Res 1998; 22: 1161-64.
121. Nosova T, Jokelainen K, Kaihovaara P, et al. Ciprofloxacin administration decreases enhanced ethanol elimination in ethanol-fed rats. Alcohol Alcohol 1999; 34: 48-54.
122. Tillonen J, Homann N, Rautio M, et al. Ciprofloxacin decreases the rate of ethanol elimination in humans. Gut 1999; 44: 347-52.
123. Tillonen J, Väkeväinen S, Salaspuro V, et al. Metronidazole increases intracolonic but not peripheral blood acetaldehyde in chronically ethanol treated rats. Alcohol Clin Exp Res, 2000; 24: 570-5.
124. Visapää J-P, Tillonen J, Salaspuro M. Microbes and mucosa in the regulation of intracolonic acetaldehyde concentration during ethanol challenge. Alcohol Alcohol 2002; 37: 322-6.
125. Larsen JA. Extrahepatic metabolism of ethanol in man. Nature 1959; 184: 1236.
126. Larsen JA, Tygstrup N, Winkler K. The significance of the extrahepatic elimination of ethanol in determination of hepatic blood flow by means of ethanol. Scand J Clin Lab Invest 1961; 13: 116-21.
127. Huang M-T, Huang C-C, Chen M-Y. In vivo uptake of ethanol and release of acetate in rat liver and GI. Life Sci 1993; 53: 165-70.
128. He SM, Lambert B. Acetaldehyde-induced mutation at the hprt locus in human lymphocytes in vitro. Environ Mol Mutagen 1990; 16: 57-63.
129. Helander A, Lindahl-Kiessling K. Increased frequency of acetaldehyde-induced sister chromatid exchanges in human lymphocytes treated with an aldehyde dehydrogenase inhibitor. Mutat Res 1991; 264: 103-7.
130. Obe G, Jonas R, Schmidt S. Metabolism of ethanol in vitro produces a compound which induces sister-chromatid exchanges in human peripheral lymphocytes in vitro: acetaldehyde not ethanol is mutagenic. Mutat Res 1986; 174: 47-51.
131. 6-methylguanine transferase. Carcinogenesis 1988; 9: 761-6.
132. Fang JL, Vaca CE. Development of a 32P-postlabelling method for the analysis of adducts arising through the reaction of acetaldehyde with 2′-deoxyguanosine-3′- monophosphate and DNA. Carcinogenesis 1995; 16: 2177-85.
133. Fang JL, Vaca CE. Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers. Carcinogenesis 1997; 18: 627-32.
134. Matsuda T, Terashima I, Matsumoto Y, et al. Effective utilization of N2-ethyl-2′-deoxyguanosine triphosphate during DNA synthesis catalyzed by mammalian replicative DNA polymerases. Biochemistry 1999; 38: 929-35.
135. Väkeväinen S, Tillonen J, Agarwal DP, et al. High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient subjects: strong evidence for the local carcinogenic action of acetaldehyde. Alcohol Clin Exp Res 2000; 24: 873-7.
136. Shaw S, Jayatilleke E, Herbert V, et al. Cleavage of folates during ethanol metabolism. Biochem J 1989; 257: 277-80.
137. Homann N, Tillonen J, Salaspuro M. Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency. Int J Cancer 2000; 86(2): 169-73.
138. Homann N, Kärkkäinen P, Koivisto T, et al. Effects of acetaldehyde on cell regeneration and differentiation of the upper gastrointestinal tract mucosa. J Natl Cancer Inst 1997; 89: 1692-7.
139. Woutersen RA, Appelmann LM, Van Garderen-Hoetmer A, et al. Inhalation toxicity of acetaldehyde in rats. III. Carcinogenicity study. Toxicology 1986; 41: 213-31.
140. Feron VJ, Kruysse A, Woutersen RA. Respiratory tract tumours in hamsters exposed to acetaldehyde vapor alone or simultaneously to benzo(a)pyrene or diethyl-nitrosamine. Eur J Cancer Clin Oncol 1982; 18: 13-31.
141. Koivisto T, Salaspuro M. Effects of acetaldehyde on brush border enzyme activities in human colon adenocarcinoma cell line Caco-2. Alcohol Clin Exp Res 1997; 21: 1599-05.
142. Koivisto T, Salaspuro M. Acetaldehyde alters proliferation, differentation and adhesion properties of human colon adenocarcinoma cell line Caco-2. Carcinogenesis 1998; 19: 2031-36.
143. Tanabe H, Ohhira M, Ohtsubo T, et al. Genetic polymorphism of aldehyde dehydrogenase 2 in patients with upper aerodigestive cancer. Alcohol Clin Exp Res 1999; 23: 17S-20S.
144. Väkeväinen S, Tillonen J, Salaspuro M. 4-Methylpyrazole decreases salivary acetaldehyde levels in ALDH2-deficient subjects but not in subjects with normal ALDH2. Alcohol Clin Exp Res 2001; 25: 829-834.
145. Sprince H, Parker CM, Smith GG, et al. Protection against acetaldehyde toxicity in the rat by L-cysteine, thiamine and L-2-methylthiazolidine-4-carboxylic acid. Agents Actions 1974; 4: 125-30.
146. Salaspuro V, Hietala J, Kaihovaara P, et al. Removal of acetaldehyde from saliva by a slow-release buccal tablet of L-cysteine. Int J Cancer 2002; 97: 361-4.
147. Roncucci L, Di Donato P, Carati L, et al. Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Dis Colon Rectum 1993; 36: 227-34.