Incorporation and/or adduction of formic acid with DNA in vivo studied by HPLC–AMS

The contribution of incorporation and/or adduction of formic acid with liver DNA in mouse was investigated using accelerator mass spectrometry CAMS) associated with high performance liquid chromatography (HPLC). Four kinds of 5'-formylated adducts, which were prepared by the reaction of formic acid and deoxyribonucleosides in vitro, were used as references for the HPLC-AMS analysis of in vivo adduction. After the administration of sodium C-14-formate to mice, the liver DNA pellets were isolated and enzymatically digested to deoxyribonucleosides. A precise analysis of the hydrolysate by HPLC-AMS indicates that a majority of formic acid incorporates directly into DNA, whereas less than 1.5% might form instable formylated DNA adducts in vivo. The results greatly support the important perspective that formic acid is not carcinogenic. Moreover, this study demonstrates that a combination of HPLC with AMS is an essential means for the evaluation of DNA adduction. (C) 2009 Elsevier B.V. All rights reserved.