Urinary arsenic speciation and porphyrins in C57Bl/6J mice chronically exposed to low doses of sodium arsenate.
Arsenic has been classified as a human carcinogen based on epidemiological data however the mechanism of its carcinogenicity is still unclear. Urinary biomarkers for chronic arsenic exposure would be valuable as an early warning indicator for timely interventions. In this study, young female C57Bl/6J mice were given drinking water containing 0, 100, 250 and 500 microg Asv/L as sodium arsenate ad libitum for 12 months. Urine was collected bimonthly for urinary arsenic methylation assay and porphyrin analysis. All detectable arsenic species showed strong linear correlation with administered dosage and the arsenic methylation patterns were similar in all three treatment groups. No significant changes of methylation patterns were observed over time for either the control or test groups. Urinary coproporphyrin III was significantly increased in the 8th month in 250 and 500 microg/L groups and remained significantly dose-related after 10 and 12 months. Coproporphyrin I also showed a significant dose-response relationship after 12 months. Our results confirm that urinary arsenic is a useful biomarker for internal dose. The alteration of porphyrin profile suggests that arsenic can affect the heme metabolism and this may occur prior to the onset of arsenic induced carcinogenesis.
National Research Centre for Environmental Toxicology (EnTox), The University of Queensland, 39 Kessels Road, Coopers Plains, Brisbane, Queensland 4108, Australia.
Huijie
H
Wu
K
K
Manonmanii
Paul K S
PK
Lam
Shu-Huei
SH
Huang
Jian Ping
JP
Wang
Jack C
JC
Ng
D000284:Administration, Oral; D000818:Animals; D001149:Arsenates / Q000008:administration & dosage / Q000633:toxicity*; D001151:Arsenic / Q000145:classification / Q000652:urine*; D020261:Arsenic Poisoning / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D011166:Porphyrins / Q000145:classification / Q000652:urine*; D014881:Water Supply
D001149:Arsenates; D015415:Biomarkers; D002273:Carcinogens; D011166:Porphyrins; C009277:sodium arsenate; D001151:Arsenic