In vivo formation of chromium(V) in chick embryo liver and red blood cells.
In order to understand the possible role of reactive intermediates in the formation of tissue-specific DNA damage by chromium(VI), electron paramagnetic resonance spectroscopy was used to study the in vivo formation of chromium(V) in the liver and red blood cells of 14 day chick embryos following treatment with chromium(VI). In vivo administration of sodium dichromate onto the inner shell membrane of 14 day chick embryos resulted in the formation of a persistent chromium(V) species in liver cells (g = 1.987). The intensity of the chromium(V) signal in liver cells plateaued at 70 min and persisted for 240 min after treatment with chromium(VI). The dependence of chromium(V) formation on the dose of sodium dichromate administered to the embryo was clearly different in liver versus red blood cells. Chromium(V) was detected in red blood cells only at high doses of sodium dichromate (0.50-0.60 mmol/kg), whereas chromium(V) was undetectable in red blood cells at lower doses of sodium dichromate (0.10-0.30 mmol/kg) which produced clear evidence for chromium(V) in liver. Uptake studies showed that total chromium levels in red blood cells were 10-fold greater than in liver cells, and that up to 10% of the total chromium existed as chromium(V) in liver and red blood cells in vivo. Depletion of glutathione by pretreatment of embryos with L-buthionine-S,R-sulfoximine (BSO) for 24 h prior to treatment with a high dose of sodium dichromate (0.60 mmol/kg) caused both a decrease in the levels of chromium(V) species produced and a decrease of chromium uptake into red blood cells 50 min after treatment. At this high dose of chromium(VI), BSO pre-treatment had no effect on the level of the chromium(V) or on chromium uptake into liver cells after a 70 min incubation period. Thus, the concentration of chromium(V) inside the cell correlated with the levels of chromium taken up into the cell. Chromium(V) may be the form of chromium which is responsible for induction of DNA damage following in vivo administration of sodium dichromate.
Liebross
R H
RH
Department of Chemistry, Dartmouth College, Hanover, NH 03755.
Wetterhahn
K E
KE
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D002478:Cells, Cultured; D002642:Chick Embryo; D002840:Chromates / Q000633:toxicity; D002857:Chromium / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology
D000963:Antimetabolites; D002840:Chromates; D002857:Chromium; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C016104:sodium bichromate; D005978:Glutathione