Chronic alcoholism is associated with increased can-and colonic epithelial cell dysplasia in ulcerative colitis cer risk that may be related to ethanol-induced alter-patients. 3 Pretreatment of folate-deficient rats with diations in methionine and deoxynucleotide metabolism. methylhydrazine resulted in a threefold increase in the These metabolic relationships were studied in micropigs incidence of neoplasia of the colonic epithelium as fed diets for 12 months that contained 40% ethanol or compared with rats fed folate-adequate diets.4 Others cornstarch control with adequate folate. Ethanol feed-demonstrated increased induction of rectal neoplasms ing altered methionine metabolism without changing in dimethylhydrazine-treated rats after ethanol-conmean terminal liver folate levels. After initial equilibrataining diets in association with increased mucosal action to diet, ethanol feeding significantly increased cumulation of acetaldehyde.5 As reviewed, 6 several epimonthly serum homocysteine levels while reducing sedemiological studies found an association of excessive rum methionine levels over the time course of the experiment. After 12 months, hepatic methionine synthase ac-alcohol consumption and increased risk of oropharyntivity and the ratio of S-adenosylmethionine (SAM) to geal, esophageal, and colorectal cancer. Two separate S-adenosylhomocysteine (SAH) were significantly re-large studies linked the relative risk of colorectal canduced in ethanol-fed animals, whereas the ratio of liver cer among consumers of alcohol to dietary folate intake, deoxyuridine triphosphate (dUTP) to deoxythymidine one study showing the greatest risk of rectal cancer triphosphate (dTTP) was increased and correlated in-among men consuming excessive alcohol and low di- The relationship between folate deficiency and alcopairment of methionine synthase activity, resulting in hol intake as cancer risk factors may reflect the biodeoxynucleoside triphosphate (dNTP) imbalance, in-chemical interactions between ethanol, folate, and mecreased apoptosis, and regenerative proliferation. These thionine metabolism.9 In addition to direct oxidative biochemical alterations may provide a promoting envi-destruction of the folic acid molecule by acetaldehyde, ethanol feeding of rats caused significant reduction of Both folate deficiency and chronic alcoholism are hepatic methyltetrahydrofolate/homocysteine methylknown risk factors for carcinogenesis. Supplemental transferase (methionine synthase) activity with comfolic acid improved bronchial dysplasia in smokers, 1 pensatory increase of betaine/homocysteine methylcervical dysplasia in women using oral contraceptives, 2 transferase activity.11-13 Ethanol-induced alterations in folate and methionine metabolism could be relevant to carcinogenesis through decreased availability of Abbreviations: dNTP, deoxynucleoside triphosphate; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; dUTP, deoxyuridine triphosphate; methyl groups for DNA methylation 14 or by altered regdTTP, deoxythymidine triphospha...

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Chronic alcoholism is associated with increased can-and colonic epithelial cell dysplasia in ulcerative colitis cer risk that may be related to ethanol-induced alterpatients. 3 Pretreatment of folate-deficient rats with diations in methionine and deoxynucleotide metabolism. methylhydrazine resulted in a threefold increase in the These metabolic relationships were studied in micropigs incidence of neoplasia of the colonic epithelium as fed diets for 12 months that contained 40% ethanol or compared with rats fed folate-adequate diets. 4 Others cornstarch control with adequate folate. Ethanol feeddemonstrated increased induction of rectal neoplasms ing altered methionine metabolism without changing in dimethylhydrazine-treated rats after ethanol-conmean terminal liver folate levels. After initial equilibrataining diets in association with increased mucosal action to diet, ethanol feeding significantly increased cumulation of acetaldehyde. 5 As reviewed, 6 several epimonthly serum homocysteine levels while reducing sedemiological studies found an association of excessive rum methionine levels over the time course of the experiment. After 12 months, hepatic methionine synthase acalcohol consumption and increased risk of oropharyntivity and the ratio of S-adenosylmethionine (SAM) to geal, esophageal, and colorectal cancer. Two separate S-adenosylhomocysteine (SAH) were significantly relarge studies linked the relative risk of colorectal canduced in ethanol-fed animals, whereas the ratio of liver cer among consumers of alcohol to dietary folate intake, deoxyuridine triphosphate (dUTP) to deoxythymidine one study showing the greatest risk of rectal cancer triphosphate (dTTP) was increased and correlated inamong men consuming excessive alcohol and low diversely with methionine synthase activity. These findetary folate 7 and the other showing the greatest inciings were associated with increased frequency of dence of colorectal adenomas in those consuming more hepatocytes with apoptotic bodies and positivity for prothan 30 g alcohol (2 drinks) daily with low intakes of liferating cell nuclear antigen (PCNA) in livers from ethanol-fed minipigs. These studies suggest that chronic foods containing folate or methionine. 8 ethanol feeding perturbs methionine metabolism by im-The relationship between folate deficiency and alcopairment of methionine synthase activity, resulting in hol intake as cancer risk factors may reflect the biodeoxynucleoside triphosphate (dNTP) imbalance, inchemical interactions between ethanol, folate, and mecreased apoptosis, and regenerative proliferation. These thionine metabolism. 9 In addition to direct oxidative biochemical alterations may provide a promoting envidestruction of the folic acid molecule by acetaldehyde, 10 ronment for carcinogenesis during long-term ethanol exthree different groups have shown that long-term posure. (HEPATOLOGY 1996;23:497-505.) ethanol feeding of rats caused significant reduction of Both folate deficiency and chronic alcoholism are hepatic methyltetrahydrofolate/homocy...

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