Journal Article

Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in Min mice

Sahar Sibani, Stepan Melnyk, Igor P. Pogribny, Wei Wang, Francois Hiou-Tim, Liyuan Deng, Jacquetta Trasler, S.Jill James and Rima Rozen

in Carcinogenesis

Volume 23, issue 1, pages 61-65
Published in print January 2002 | ISSN: 0143-3334
Published online January 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.1.61
Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in Min mice

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Several epidemiological studies have suggested a modulatory effect of dietary folate intake on the risk of colorectal cancer. The molecular basis for this inverse association is not clearly understood, but may involve alterations in DNA methylation. In this study, we examined the levels of methylation intermediates [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)] and of global DNA methylation in the pre-neoplastic small intestine of Min (multiple intestinal neoplasia) mice. We also studied the effect of folate/choline deficiency on these parameters and on tumor multiplicity in this animal model. In folate-adequate Min mice, we identified positive linear correlations between SAM or SAH and tumor numbers (R2 = 0.38, P < 0.005; R2 = 0.26, P = 0.025, respectively). A positive correlation between global DNA hypomethylation and tumor multiplicity was also observed (R2 = 0.29, P = 0.014). These three biochemical determinants (SAM, SAH and DNA hypomethylation) may, therefore, serve as early markers of cell transformation. Folate/choline deficiency, however, did not produce a consistent effect on tumor numbers in three separate experiments. As an increase in tumor numbers was observed only in folate- and choline-deficient mice with low levels of SAM and DNA hypomethylation, the modulatory role of folate may be dependent on the transformation state of the cell.

Keywords: Min, multiple intestinal neoplasia; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine.

Journal Article.  3665 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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