Nickel(II)-mediated oxidative DNA base damage in renal and hepatic chromatin of pregnant rats and their fetuses. Possible relevance to carcinogenesis.
DNA base damage was studied in renal and hepatic chromatin of nickel(II)-injected pregnant female F344/NCr rats and their fetuses under conditions leading to initiation of sodium barbital-promotable renal tumors, but not liver tumors, in the male offspring. Pregnant rats were given a total of 90 or 180 mumol of nickel(II) acetate/kg body wt in a single ip dose on day 17 or in 2 or 4 ip doses between days 12 and 18 of gestation. Control rats received 180 mumol of sodium acetate/kg body wt. The animals were killed 24 or 48 h after the last injection. Chromatin was isolated from livers and kidneys from both adults and fetuses and analyzed by gas chromatography/mass spectrometry with selected ion monitoring. Eleven products derived from the purine and pyrimidine bases in DNA bases were identified and quantified. These were the following: 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin, 5-(hydroxymethyl)uracil, cytosine glycol, thymine glycol, 5,6-dihydroxycystosine, 4,6-diamino-5-formamidopyrimidine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 8-hydroxyadenine, 2-hydroxyadenine, and 8-hydroxyguanine (8-OH-Gua). Nickel(II) exposure increased the content of these products, especially those derived from purines, in both renal and hepatic chromatin of pregnant rats. The major difference between these two organs was the content of 8-OH-Gua, which increased greatly in the kidney but remained unchanged in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Kasprzak
K S
KS
Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, Maryland 21702.
Diwan
B A
BA
Rice
J M
JM
Misra
M
M
Riggs
C W
CW
Olinski
R
R
Dizdaroglu
M
M
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002843:Chromatin / Q000187:drug effects*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D007668:Kidney / Q000737:chemistry / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D009532:Nickel / Q000633:toxicity*; D010084:Oxidation-Reduction; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D002843:Chromatin; D009532:Nickel; D004247:DNA