Urinary arsenic methylation and porphyrin profile of C57Bl/6J mice chronically exposed to sodium arsenate.
Arsenic interferes with the function of enzymes responsible for haem biosynthesis leading to alteration in the porphyrin profile. In this study, young female C57Bl/6J mice were given drinking water containing 0, 100, 250 and 500 microg As(V)/L as sodium arsenate ad libitum for 24 months. 24 h pooled urine samples were collected bimonthly for urinary arsenic methylation and porphyrin analyses by HPLC-ICP-MS and HPLC respectively. The levels of total arsenic were significantly dose related except for the 2nd month interval. No significant differences in the urinary arsenic methylation pattern between control and test groups were observed. Coproporphyrin I (Copro I) showed a significant dose-response relationship after 12, 14 and 20 months of exposure. Significant differences in the levels of coproporphyrin III (Copro III) were observed in the 8th month in 250 and 500 microg/L treatment groups and the dose-response pattern was maintained after 10 and 12 months. Our results suggest that urinary arsenic is a useful biomarker for internal dose, and that urinary coproporphyrin can be used as an early warning biomarker of effects before the onset of cancer.
Krishnamohan
Manonmanii
M
National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Road, Coopers Plains, Brisbane, Qld 4108, Australia.
Wu
Hui-Jie
HJ
Huang
Shu-Huei
SH
Maddelena
Robyn
R
Lam
Paul K S
PK
Moore
Michael R
MR
Ng
Jack C
JC
D000818:Animals; D001149:Arsenates / Q000493:pharmacokinetics* / Q000633:toxicity; D001151:Arsenic / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000139:chemically induced / Q000652:urine; D011166:Porphyrins / Q000652:urine*
D001149:Arsenates; D015415:Biomarkers; D002273:Carcinogens; D011166:Porphyrins; C009277:sodium arsenate; D001151:Arsenic