Oxidative DNA base damage and its repair in kidneys and livers of nickel(II)-treated male F344 rats

later days, except for 5-hydroxyhydantoin. In kidneys, rosilane were obtained from the Pierce Chemical Company (Rockford, IL). the levels of only three damaged bases, 8-oxoguanine, 5- Tris, EDTA, Chelex-100 resin (200‐400 mesh), Triton X-100, sucrose, hydroxyhydantoin and 5,6-dihydroxyuracil were increased phenylmethane-sulfonyl fluoride, dithiothreitol, isobarbituric acid (5-hydrosignificantly (by 31, 73 and 60%, respectively) and one xyuracil; 5-OH-Ura) and 5-(hydroxymethyl)uracil (5-OHMe-Ura) were purchased from Sigma Chemical Co. (St Louis, MO). Thymine-α,α,α,6- 2 H4 was base, 8-oxoadenine, was increased by 26%, just below obtained from Merck and Co., Inc./Isotopes (Montreal, Canada). 5-Hydroxysignificance, all in terms of overall adjusted means for days 5-methylhydantoin (5-OH-5-Me-Hyd), dialuric acid, isodialuric acid [5,61‐14 post-injection. Hence, unlike those in the liver, the dihydroxyuracil (5,6-diOH-Ura)], 5-hydroxycytosine (5-OH-Cyt), 4,6-diamrenal increases persisted for 14 days. The results reveal a ino-5-formamidopyrimidine (FapyAde), 7,8-dihydro-8-oxoadenine (8-oxotissue specific response to Ni(II)-mediated oxidative DNA Ade), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), 7,8-dihydro-8-oxoguanine (8-oxo-Gua), 5-hydroxy-5-methylhydantoin-1,3- 15 N2-2- 13 C, base damage with apparently faster DNA repair in liver dialuric acid-1,3- 15 N2-2,4- 13 C2, 5-hydroxyuracil-1,3- 15 N2-2- 13 C, 5-(hydroxythan in kidney, the main target of Ni(II) carcinogenicity. methyl)uracil-2,4- 13 C2-α,α- 2 H2, 5-hydroxycytosine-1,3- 15 N2-2- 13 C, 5,6- dihydroxyuracil-1,3-15N2-2-13C, 4,6-diamino-5-formamidopyrimidine-1,3-15N-213C-(5-aminoformyl-15N,2H), 7,8-dihydro-8-oxoadenine-1,3,7-15N3-2,8-13C2, 2,6-diamino-4-hydroxy-5- formamidopyrimidine-1,3-15N2-(5-aminoformyl-15N)