Uthus Eric O, Davis Cindy
United States Department of Agriculture, ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, USA.
Biol Trace Elem Res. 2005 Feb;103(2):133-45. doi: 10.1385/BTER:103:2:133.
Cell culture studies have suggested that arsenic exposure results in decreased S-adenosylmethionine (SAM), causing DNA hypomethylation. Previously, we have shown that hepatic SAM is decreased and/or S-adenosylhomocysteine increased in arsenic-deprived rats; these rats tended to have hypomethylated DNA. To determine the effect of dietary arsenic on dimethylhydrazine (DMH)-induced aberrant crypt formation in the colon, Fisher 344 weanling male rats were fed diets containing 0, 0.5, or 50 microg As (as NaAsO2)/g. After 12 wk, dietary arsenic affected the number of aberrant crypts (p<0.02) and aberrant crypt foci (p<0.007) in the colon and the amount of global DNA methylation (p<0.04) and activity of DNA methyltransferase (DNMT) (p<0.003) in the liver. In each case, there were more aberrant crypts and aberrant crypt foci, a relative DNA hypomethylation, and increased activity of DNMT in the rats fed 50 microg As/g compared to those fed 0.5 microg As/g. The same phenomenon, an increased number of aberrant crypts and aberrant crypt foci, DNA hypomethylation, and increased DNMT tended to hold when comparing rats fed the diet containing no supplemental arsenic compared to rats fed 0.5 microg As/g. The data suggest that there is a threshold for As toxicity and that possibly too little dietary As could also be detrimental.
细胞培养研究表明，接触砷会导致S-腺苷甲硫氨酸（SAM）减少，从而引起DNA低甲基化。此前，我们已表明，缺砷大鼠肝脏中的SAM减少和/或S-腺苷同型半胱氨酸增加；这些大鼠往往存在DNA低甲基化。为了确定膳食砷对二甲基肼（DMH）诱导的结肠异常隐窝形成的影响，给Fisher 344断奶雄性大鼠喂食含0、0.5或50微克砷（以NaAsO2形式）/克的饲料。12周后，膳食砷影响结肠中异常隐窝数量（p<0.02）和异常隐窝灶数量（p<0.007），以及肝脏中整体DNA甲基化水平（p<0.04）和DNA甲基转移酶（DNMT）活性（p<0.003）。在每种情况下，与喂食0.5微克砷/克的大鼠相比，喂食50微克砷/克的大鼠有更多的异常隐窝和异常隐窝灶、相对的DNA低甲基化以及DNMT活性增加。当比较未补充砷的饲料喂养的大鼠与喂食0.5微克砷/克的大鼠时，同样出现了异常隐窝和异常隐窝灶数量增加、DNA低甲基化以及DNMT增加的现象。数据表明，砷毒性存在一个阈值，而且可能膳食中砷含量过低也会有害。
