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ARSENIC INDUCTION OF HEME OXYGENASE AS A BIOMARKER
Citation:
Kitchin, K T., L. M. Del Razo, J L. Brown, W L. Anderson, E M. Kenyon, AND D J. Thomas. ARSENIC INDUCTION OF HEME OXYGENASE AS A BIOMARKER. Presented at 4th Int'l Conference on Arsenic Exposure & Health Effects, San Diego, CA, June 18-22, 2000.
Description:
Useful biomarkers of arsenic effects in both experimental animals and humans are needed. Arsenate and arsenite are good inducers of rat hepatic and renal heme oxygenase (HO); monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) are not. Therefore, HO enzyme induction should theoretically be an excellent biomarker of biologically active arsenite concentration .
Liver and kidney inorganic arsenic, MMA and DMA concentrations and HO enzyme activities were determined 2 to 144 hours after oral administration of 100 umoles/kg of sodium arsenite to adult female Sprague-Da\'Vley rats. In rat liver the mean inorganic arsenic concentrations were 0.11,2.15,1.85,1.86,1.82,0.68,0.51,0.20 and 0.10 ug/g at 0, 2, 4, 8, 16, 24,48, 72 and 144 hours after arsenite administration, respectively. At these sarne time points, rat hepatic HO activities were 1.0, 10.8, 6.8, 16.3, 21.2, 5.2, 3.8, 0.8 anti 0-5 times control HO values. At these time points 86, 46, 61, 66, 80, 89, 95, 97 and 98% of the total rat liver arsenic was present as DMP., which does not induce HO.
A hepatic concentration of 0.49 ug/g of additional exogenous inorganic arsenic was present before or at the time of HO enzyme induction. In rat kidney lower inorganic arsenic concentrations and less HO enzyme induction occurred after oral arsenite administration. This study links tissue arsenic dosimetry with a biological effect (HO enzyme induction) in two target tissues for arsenic-induced carcinogenesis.
This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.