Enhancement by L-histidine of nickel(II)-induced DNA-protein cross-linking and oxidative DNA base damage in the rat kidney.
Formation of DNA-protein cross-links and oxidatively damaged DNA bases was investigated with the use of alkaline elution and gas chromatography/mass spectrometry techniques in the nuclei from kidneys of rats 3 and 18 h after a single iv injection of the NiII(His)2 complex (NiHis), nickel(II) acetate (NiAcet), or L-histidine (His). Administration of 20 mumol of NiHis/kg body wt caused the formation of DNA-protein cross-links and significantly increased levels of oxidatively damaged DNA bases, including 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua; 3.5-fold vs the control value) 3 h postinjection and 8-oxoguanine (2.6-fold), cytosine glycol (2.5-fold), 8-oxoadenine (2-fold), and FapyGua (1.9-fold) 18 h postinjection. Injection of 20 mumol of NiAcet/kg body wt enhanced the cross-linking to a lesser extent than NiHis and did not significantly increase the amounts of modified DNA bases over the control levels. Forty micromoles of His per kilogram body wt alone caused a marked DNA-protein cross-linking effect and increased the amount of 4,6-diamino-5-formamidopyrimidine (2-fold vs the control) 3 h, but not 18 h, after treatment. The DNA base derivatives found were typical products of hydroxyl radical (.OH) attack on DNA. Formation of the cross-links may also be attributed to .OH, although other mechanisms, e.g., formation of ternary complexes of Ni(II), cannot be excluded. The present in vivo study confirms the conclusion of our former in vitro experiments that His enhances Ni(II)-mediated oxidative damage to DNA and chromatin.(ABSTRACT TRUNCATED AT 250 WORDS)
Misra
M
M
Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, Maryland 21702-1201.
Olinski
R
R
Dizdaroglu
M
M
Kasprzak
K S
KS
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000032:analysis / Q000187:drug effects*; D004249:DNA Damage; D019286:Endopeptidase K; D008401:Gas Chromatography-Mass Spectrometry; D006639:Histidine / Q000633:toxicity*; D006868:Hydrolysis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009532:Nickel / Q000633:toxicity*; D010084:Oxidation-Reduction; D011506:Proteins / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D012697:Serine Endopeptidases; D013050:Spectrometry, Fluorescence
D003432:Cross-Linking Reagents; D011506:Proteins; D006639:Histidine; D009532:Nickel; D004247:DNA; D012697:Serine Endopeptidases; D019286:Endopeptidase K