Progression of prostate carcinogenesis and dietary methyl donors: Temporal dependence

Insufficient dose of dietary methyl groups are associated with a host of conditions ranging from neural tube defects to cancer.Onthe other hand, it is not certain what effect excess dietary methyl groups could have on cancer. This is especially true for prostate cancer, a disease that is characterized by increasing DNA methylation changes with increasing grade of the cancer. In this three-part study in animals, we look at (i) the effect of excess methyl donors on the growth rate of prostate cancer in vivo, (ii) the ability of 5-aza-2′- deoxycytidine (AdC), a demethylating agent, to demethylate in the presence of excess dietary methyl donors, and (iii) the effect of in utero feeding of excess methyl donors to the later onset of prostate cancer. The results show that when mice are fed a dietary excess of methyl donors, we do not see (i) an increase in the growth rate of DU-145 and PC-3 xenografts in vivo, or (ii) interference in the ability of AdC to demethylate the promoters of androgen receptor or Reprimo of prostate cancer xenografts but (iii) a protective effect on the development of higher grades of prostate cancer in the "Hi-myc" mouse model of prostate cancer which were fed the increased methyl donors in utero. We conclude that the impact of dietary methyl donors on prostate cancer progression depends upon the timing of exposure to the dietary agents. When fed before the onset of cancer, that is, in utero, excess methyl donors can have a protective effect on the progression of cancer.