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ARSENITE 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. ARSENITE INDUCTION OF HEME OXYGENASE AS A BIOMARKER. Presented at 1st Int'l Symp on HO/CO, New York City, NY, 7/14-17/2000.
Description:
ARSENITE INDUCTION OF HEME OXYGENASE AS A BIOMARKER
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 110 enzyme activities were determined 2 to 144 hours after oral administration of 100 umoles/kg of sodium arsenite to adult female Sprague-Dawley 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 uglg at 0, 2, 4, 8, 16, 24, 48, 72 and 144 hours after arsenite administration, respectively. At these same time points, rat hepatic HO activities were 1.0, 10.8' 6.8, 16.3, 21.2,5.2, 3.8, 0.8 and 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 DMA, which does not induce HO.
A hepatic Ct)ncentration of 0.49 uglg 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-jnduced carcinogenesis.
This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.