Use Of Urinary Porphyrin Profiles As An Early
Warning Biomarker For Monomethylarsonous
Acid (MMA III ) Exposure
Author(s)
M. Krishnamohan, S.-H. Huang, R. Maddalena, J.-P. Wang,
P. Lam, J. C. Ng & M. R. Moore
Abstract
Although it is well known that arsenic is toxic and that Arsenic is carcinogenic,
the mechanism underlying this carcinogenesis is unknown. Our laboratories have
established a model that produces multi-organ tumours in mice following
extended exposure to arsenic in drinking water. Until recently the metabolism of
arsenic was thought to be a detoxification process. Recent studies have shown
that Monomethylarsonous acid (MMA III ) is the toxic intermediate of arsenic
metabolism. It is a more potent cytotoxin and genotoxin than As III and As V , and
is believed to be the proximal carcinogen. Exposure to arsenic is known to affect
the activity of the enzymes of haem biosynthesis. We evaluated the use of
urinary porphyrin profiles as an early warning biomarker for arsenic
carcinogenicity. Young female mice were given drinking water containing
arsenic as MMA III ad libitum. 24h urine samples were collected at various time
intervals for up to 48 weeks for urinary arsenic accumulation by HPLC-ICPMS
and urinary porphyrin measurement by HPLC. Dimethylarsinic acid (DMA V )
was the major metabolite excreted and it showed significant dose-dependent
increase at each time point and exposure dependent increase over 48 weeks.
Porphyrin levels appeared to be age dependent. The results indicate that the
urinary porphyrin concentration has the potential for use as an early warning
indicator of chronic arsenic exposure prior to the onset of arsenic carcinogenesis.
Keywords: arsenic, porphyrins, haem synthesis, Monomethylarsonous acid,
biomarkers, cancer.
Keywords
arsenic, porphyrins, haem synthesis, Monomethylarsonous acid,
biomarkers, cancer.
Related Book
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