|Kim, Kyong chol|
Submitted to: American Association of Cancer Research Meeting
Publication Type: Abstract only
Publication Acceptance Date: 4/30/2008
Publication Date: 5/30/2008
Citation: Sauer, J., Jang, H., Kim, K., Keyes, M.K., Smith, D., Choi, S. 2008. Aging, chronic alcohol consumption, and low folate intake are determinants of genomic DNA methylation in the liver and colon of mice. American Association of Cancer Research Meeting. Interpretive Summary:
Technical Abstract: Advanced age and chronic alcohol consumption are important risk factors in the development of colon and liver cancer. Both factors are known to be associated with altered DNA methylation. Inadequate folate intake can also derange biological methylation pathways. We investigated the effects of aging, chronic alcohol consumption, and low dietary folate on genomic DNA methylation in mouse colon and liver. Old (18 months; n=70) and young (4 months; n=70) male C57BL/6 mice were randomly divided into 3 groups and pair-fed either an alcohol-containing (18% of energy), an alcohol-containing folate-reduced (0.25 mg folate/L) or an isocaloric control Lieber-DeCarli diet (0.5 mg folate/L) for 5 or 10 weeks. Genomic DNA methylation was analyzed using liquid chromatography/electrospray ionization/MS. Genomic DNA methylation decreased in colon of old mice compared with young mice (p<0.01) for all dietary groups. DNA methylation in old mice decreased consuming diets containing 18% alcohol (p=0.06) and 18% alcohol with low folate (p<0.01) for 5 weeks, however, this effect disappeared after 10 weeks. In young mice, the 18% alcohol diet reduced DNA methylation after 10 weeks compared to the control diet (p<0.05). In the liver, old mice had a tendency toward a lower DNA methylation compared to young mice (p=0.09). There was no diet effect in the livers of old mice, whereas the alcohol diets lowered DNA methylation after 10 weeks in the young (Ptrend=0.05). In conclusion, changes in genomic DNA methylation in mouse colon and liver suggest an epigenetic response to the major cancer risk factors aging and alcohol consumption.