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.