Influence of antimonite, selenite, and mercury on the toxicity of arsenite in primary rat hepatocytes.
The long-term toxicity of arsenic (As) as a result of exposure to contaminated drinking water might be modified by coinciding exposures to elements like selenium, antimony, or mercury. In this study the influence of tetravalent selenite, trivalent antimonite, and divalent mercury was investigated in vitro using cultured primary rat hepatocytes. The cell vitality was assessed in the 3-[4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] (MTT), assay with concurrent exposures of the cells to up to 50 microM sodium arsenite(III) and a potential modifier [50 microM sodium(IV) selenite, 10 microM antimony(III) chloride, 25 microM mercuric(II) chloride], which indicated an additive increase in the combined cytotoxicity. Sodium arsenite was tested for genotoxicity in the micronucleus test in a concentration range of 0.25 up to 7.5 microM. In this range, the MTT conversion was at least 80%, indicating high cell viability. Adose-dependent induction of micronuclei was observed. The lowest concentration causing a significantly elevated frequency of micronuclei was 1 microM As (p < 0.05). A significant influence (i.e., reduction of the combined genotoxicity as a result of the presence of a potential modifier) was only observed for 10 and 25 microM antimony chloride (p < 0.05, Fisher's exact test). The metabolic methylation of arsenite was not affected by concurrent incubation with any of the potential modifiers.
Hasgekar
N
N
Medical Institute of General Hygiene and Environmental Health, University of Goettingen, D-37073 Goetttingen, Germany.
Beck
J P
JP
Dunkelberg
H
H
Hirsch-Ernst
K I
KI
Gebel
T W
TW
D000818:Animals; D000965:Antimony / Q000494:pharmacology*; D001151:Arsenic / Q000378:metabolism; D018053:Arsenites / Q000633:toxicity*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D008628:Mercury / Q000494:pharmacology*; D008745:Methylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018038:Sodium Selenite / Q000494:pharmacology*
D018053:Arsenites; C061374:antimonite; D000965:Antimony; D008628:Mercury; D018038:Sodium Selenite; C015001:arsenite; D001151:Arsenic