Folic Acid Intake and Arsenic Biotransformation in Mice

Richard H. Finnell, Ph.D.
Texas A&M University Health Science Center
P30ES09106 and P42ES04917

Background: In most mammals, arsenic transformation occurs by the addition of methyl groups resulting in dimethylarsinic acid being the predominant metabolite excreted in the urine. Previous research by this and other laboratories have established a link between arsenic metabolism and folate biochemistry. These researchers sought to determine if folate binding protein-1 is an important component of arsenic transformation using transgenic mice lacking the gene for the binding protein. Their experiments also investigated whether dietary folate deficiency in these mice altered arsenic biotransformation.

Advance: Dietary folate deficiency caused reduced excretion of arsenic in the urine of both the transgenic mice lacking the folate binding protein and in wild-type control mice. The transgenic mice excreted more dimethylarsinic acid than the control mice during folate deficiency but not when their diets were folate sufficient.

Implication: These results suggest that inadequate dietary folate may result in decreased transformation and excretion of arsenic. Impaired biotransformation and excretion of arsenic results in increased body retention and exposure in humans. In turn, an increase in arsenic retention is likely to increase the risk of arsenic-induced toxicities, especially in certain at-risk populations due to their genetic predisposition.

Citation: Spiegelstein O, Lu X, Le XC, Troen A, Selhub J, Melnyk S, James SJ, Finnell RH. Effects of dietary folate intake and folate binding protein-1 (Folbp1) on urinary speciation of sodium arsenate in mice. Toxicol Lett. 2003 Nov 30;145(2):167-74.