Potential urinary biomarkers for chronic arsenic exposure to C57B1/6J mice

Abstract

Arsenic has been classified as a human carcinogen based on very strong epidemiological data although the mechanism of its carcinogenicity is till largely unknown. Urinary biomarkers for chronic arsenic exposure would be valuable as an early warning indicator for timely interventions, In this study, young female C57B1/6J mice were given drinking water containing 0, 100, 250 and 500 μg Asˇ/L as sodium arsenate ad lib for 12 months. Urine was collected every two months including time zero for urinary methylation assay (i.e. speciation of inorganic arsenic and its methylated metabolites) and analyses of a range of biomarkers. All detectable arsenic species showed strong in all three groups. No significant changes of methylation pattern were observed over time for neither control nor test groups. Malondialdehyde, an index for lipid peroxidation, was not altered in the exposure groups up to 12 months. However, urinary 8-Hydroxy-2’ –deoxyguanosine, a biomarker of DNA damage, showed a significant dose-response relationship after 8 months of exposure. Urinary Coproporphyrin III, an intermediate product of heme biosynthesis, was significantly increased in the 8th month in the 250 and 500 μg/L groups and remained significantly dose-response related after 10 and 12 months of exposure. Coproporphyrin I also showed a significant dose-response relationship after 12 months. No tumors were observed in any of the animals in the control or treatment groups. The results of this study indicate that urinary arsenic could be used as a potential biomarker for internal dose and biological effects; arsenic affects heme metabolism by altering the porphyrin synthetic pathway and extra arsenic exposure could result in an increase of ROS, consequently leading to DNA damage, or even cancer. All theses effects may occur in the early stage of chronic arsenic exposure before the onset of tumorigenesis, and this finding may be of potential clinical significance.

Date of Award	4 Oct 2004
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Kwan Sing Paul LAM (Supervisor)