The relationship between nickel chloride-induced peroxidation and DNA strand breakage in rat liver.
Inorganic nickel chloride induces hepatic DNA strand breaks, chromosome aberrations, and lipid peroxidation under in vitro and in vivo conditions. The objective of this research was to determine if a relationship exists between NiCl2 genotoxicity and lipid peroxidation in vivo. Male Sprague-Dawley rats (210-250 g) were dosed with 0.56 or 0.75 mmol/kg NiCl2 subcutaneously and euthanized after specific time periods, ranging from 30 min to 24 hr. Livers were perfused and excised for the measurement of nickel content using atomic absorption spectrometry, lipid peroxidation using a thiobarbituric acid assay, and DNA strand breakage using single-stranded DNA extraction and the diaminobenzoic acid assay. The lower dose (0.56 mmol/kg) did not induce lipid peroxidation or strand breakage. The higher dose (0.75 mmol/kg) induced DNA strand breakage at 4 hr and lipid peroxidation at 12 hr in rat liver. Nickel was seen to accumulate in liver nuclei of rats receiving 0.75 mmol/kg. Deferoxamine (1 g/kg, ip, 15 min before the NiCl2 injection) completely inhibited DNA strand breakage at 4 hr but had no effect on lipid peroxidation. This suggests that lipid peroxidation is not causally related to genetic damage. NiCl2-induced DNA strand breakage may be caused by the induction of the Fenton reaction, generating hydroxyl radicals.
Stinson
T J
TJ
Institute for Environmental Studies, University of Illinois, Urbana 61801.
Jaw
S
S
Jeffery
E H
EH
Plewa
M J
MJ
D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009532:Nickel / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
C022838:nickel chloride; D009532:Nickel; D004247:DNA; D003676:Deferoxamine