Abstract
Arsenic is a proven human carcinogen. Although the mechanism of its carcinogenicity is still largely unknown, methylation is thought to have an important role to play in arsenic toxicity. In this study, urinary methylation profiles were investigated in female C57BL/6J black mice given drinking water containing 500 μg arsenate (As(V))/L, 250 μg As(V)/L, or 100 μg As(V)/L as sodium arsenate for 2 months. The concentrations of arsenic chosen reflected those in the drinking water often encountered in arsenic-endemic areas. Urine samples were collected from the mice at the end of the exposure period, and the arsenic species were analyzed by high performance liquid chromatography-inductively coupled plasma-mass spectrometry. All detectable arsenic species showed strong linear correlation with the administered dosage. The methylation patterns were similar in all three groups with a slight decrease of dimethylarsinic acid/As(V) ratio in the 500-μg/L group, which corresponded to the significantly higher arsenic retention in the tissue. The results indicate that urinary arsenic could be used as a good biomarker for internal dose and potential biological effects. Different doses of arsenic exposure could result in different degrees of methylation, excretion, and tissue retention, and this may contribute to the understanding of arsenic carcinogenicity.