CELLULAR UPTAKE AND METABOLIC REDUCTION OF PENTAVALENT TO TRIVALENT ARSENIC AS DETERMINANTS OF CYTOTOXICITY AND TRANSFORMATION
Cellular uptakes of As-73-labelled sodium arsenite (As**+3) and arsenate (As**+5) in BALB/3TE Cl A31-1-1 cells were dose-dependent, highest in the first h and decreasing thereafter. At 3 x 10**-6 M, uptake was 4-fold higher for As**+3 than As**+5. Cytotoxicity (24 and 72 h exposures) was higher for As**+3 than As**+5, but when correlated to As cell burden it showed no significant difference for the 2 forms. Both As**+3 and As**+5 induced neoplastic transformation, showing relative frequencies of 5:1. Either form of absorbed As showed > 90% recovery from cytosol after 1-24 h exposures. Exposure to As**+3 yielded 100% as As**+3 in cytosol, but As**+% yielded > 70% as As**+3, showing a high rate of intracellular metabolic reduction. No methylated metabolites were detected by ion exchange chromatography. As**+3 to As**+5 oxidation occurred in cell-free medium (30% after 24 h incubation), but less so (4%) in the presence of cells. As**+5 was recovered unchanged from cell-free medium (24 h incubation), but yielded up to 5% As**+3 when incubated with cells. Release of As**+3 by cells exposed to As**+5 was dose- dependent. Glutathion depletion by diethylmaleate inhibited reduction of As**+5 to As**+3 by these cells up to 25% of controls.
Bibliographic Reference: 26TH ANNUAL MEETING SOCIETY OF TOXICOLOGY, WASHINGTON (USA), FEB. 23-27, 1987 WRITE TO CEC LUXEMBOURG, DG XIII/A2, POB 1907 MENTIONING PAPER E 33195 ORA
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Record Number: 1989125072600 / Last updated on: 1987-12-01
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