Urinary arsenic and porphyrin profile in C57BL/6J mice chronically exposed to monomethylarsonous acid (MMAIII) for two years.
Arsenicals are proven carcinogens in humans and it imposes significant health impacts on both humans and animals. Recently monomethylarsonous acid (MMA(III)), the toxic metabolite of arsenic has been identified in human urine and believed to be more acutely toxic than arsenite and arsenate. Arsenic also affects the activity of a number of haem biosynthesis enzymes. As a part of 2-year arsenic carcinogenicity study, young female C57BL/6J mice were given drinking water containing 0, 100, 250 and 500 microg/L arsenic as MMA(III)ad libitum. 24 h urine samples were collected at 0, 1, 2, 4, 8 weeks and every 8 weeks for up to 104 weeks. Urinary arsenic speciation and porphyrins were measured using HPLC-ICP-MS and HPLC with fluorescence detection respectively. DMA(V) was a major urinary metabolite detected. Significant dose-response relationship was observed between control and treatment groups after 1, 4, 24, 32, 48, 56, 88, 96 and 104 weeks. The level of uroporphyrin in 250 and 500 microg As/L group is significantly different from the control group after 4, 8, 16, 32, 56, 72, 80, 96 and 104 weeks. Coproporphyrin I level in 500 microAs/L group is significantly different from control group after 8, 24, 32, 40, 56, 72, 80, 88 and 104 weeks. After 4 weeks the level of coproporphyrin III concentration significantly increased in all the treatment groups compared to the control except week 16 and 48. Our results show urinary DMA(V) and porphyrin profile can be used as an early warning biomarker for chronic MMA(III) exposure before the onset of cancer.
Krishnamohan
Manonmanii
M
National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Road, Coopersplains, Brisbane, Qld 4108, Australia.
Qi
Lixia
L
Lam
Paul K S
PK
Moore
Michael R
MR
Ng
Jack C
JC
D000818:Animals; D001151:Arsenic / Q000652:urine*; D015415:Biomarkers; D014408:Biomarkers, Tumor; D002851:Chromatography, High Pressure Liquid; D003306:Coproporphyrins / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000633:toxicity*; D011166:Porphyrins / Q000652:urine*; D021241:Spectrometry, Mass, Electrospray Ionization; D014578:Uroporphyrins / Q000652:urine
D015415:Biomarkers; D014408:Biomarkers, Tumor; D003306:Coproporphyrins; D009942:Organometallic Compounds; D011166:Porphyrins; D014578:Uroporphyrins; C406082:monomethylarsonous acid; C026971:coproporphyrin III; C031467:coproporphyrin I; D001151:Arsenic