Oxidative DNA base damage and its repair in kidneys and livers of nickel(II)-treated male F344 rats.
DNA base damage was assayed using gas chromatography/ mass spectrometry with selected ion monitoring (GC/MS-SIM) in renal and hepatic chromatin of male F344 rats up to 14 days after a single i.p. injection of 90 micromol Ni(II) acetate/kg body wt. Ten different damaged bases were quantified. No damage was found in either organ 12 h after Ni(II) treatment. The damage became significant only from day 1, with magnitude and persistence depending on the organ and base. In livers, levels of five DNA base products were significantly elevated over those in control rats. They were: 8-oxoguanine (by 46% at day 1 postinjection); 2,6-diamino-4-hydroxy-5-formamidopyrimidine (by 107% at day 1); 5-(hydroxymethyl)uracil (by 94% at day 1); 5,6-dihydroxyuracil (by 128% at day 1); and 5-hydroxyhydantoin (by 39% in terms of the overall adjusted means for days 1-14 post-injection). The elevation was highest at day 1 post-injection followed by a decrease at later days, except for 5-hydroxyhydantoin. In kidneys, the levels of only three damaged bases, 8-oxoguanine, 5-hydroxyhydantoin and 5,6-dihydroxyuracil were increased significantly (by 31, 73 and 60%, respectively) and one base, 8-oxoadenine, was increased by 26%, just below significance, all in terms of overall adjusted means for days 1-14 post-injection. Hence, unlike those in the liver, the renal increases persisted for 14 days. The results reveal a tissue specific response to Ni(II)-mediated oxidative DNA base damage with apparently faster DNA repair in liver than in kidney, the main target of Ni(II) carcinogenicity.
Kasprzak
K S
KS
Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, MD 21702, USA.
Jaruga
P
P
Zastawny
T H
TH
North
S L
SL
Riggs
C W
CW
Olinski
R
R
Dizdaroglu
M
M
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D007668:Kidney / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008297:Male; D009532:Nickel / Q000633:toxicity*; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344
D000085:Acetates; D009532:Nickel; D004247:DNA