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APPARENT SEXUAL DIFFERENCES IN METABOLISM OF INORGANIC ARSENIC IN HUMAN HEPATOCYTES
Styblo, M., G. A. Hamilton, E. L. LeCluyse, AND D J. Thomas. APPARENT SEXUAL DIFFERENCES IN METABOLISM OF INORGANIC ARSENIC IN HUMAN HEPATOCYTES. Presented at SOT, San Francisco, CA, March 25-29, 2001.
APPARENT SEXUAL DIFFERENCES IN METABOLISM OF INORGANIC ARSENIC IN HUMAN HEPATOCYTES. M Styblo1, G A Hamilton1, E L LeCluyse1 and D J Thomas2. 1University of North Carolina, Chapel Hill, NC, USA; 2US EPA, ORD, NHEERL, Research Triangle Park, NC, USA.
The liver is considered a major site for methylation of inorganic arsenic (iAs) in most animal species. However, little information is available about methylation of iAs in human liver. This work examined production of methylarsenic (MAs) and dimethylarsenic (DMAs) metabolites in primary cultures of human hepatocytes exposed to 0.1 to 20 mM arsenite (iAsIII), for up to 24 or 48 hours. Hepatocytes were obtained from six adult (three male and three female) donors and cultured under standard conditions for 2 to 3 days before exposure to iAsIII. Cells exposed to 0.1 mM iAsIII produced both MAs and DMAs. The average methylation rate (pmol iAs methylated by 106 cells per hour) was greater in cells obtained from female donors than in cells from male donors: 5.3 ? 0.92 vs. 3.0 ? 0.57 (Mean ? SD). The average methylation ratio (DMAs/MAs) was also greater in cells from female than from male donors: 6.6 ? 2.83 vs. 2.3 ? 0.62. The methylation patterns were strongly dependent on iAsIII concentration in the cultures. The methylation yields in both groups increased in the range of 0.1 to 0.4 mM iAsIII. However, higher concentrations of iAsIII inhibited DMAs synthesis, decreasing significantly methylation ratio. Exposure to 4 to 20 mM iAsIII resulted in inhibition of both methylation reactions. In general, hepatocytes from female donors exhibited greater methylation rates and methylation ratios than cells from male donor at the same level of exposure. These data suggest the capacity of human liver to metabolize iAs may be sex-dependent, implying that adult female liver can methylate iAs more effectively than male liver even at higher exposure levels.
(This abstract does not necessarily reflect policy of the U.S. Environmental Protection Agency.)
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
EXPERIMENTAL TOXICOLOGY DIVISION