OXIDATIVE DNA-BASE DAMAGE IN RENAL, HEPATIC, AND PULMONARY CHROMATIN OF RATS AFTER INTRAPERITONEAL INJECTION OF COBALT(II) ACETATE

DNA base damage was studied in renal, hepatic, and pulmonary chromatin of male and female F344/NCr rats that had been given either 50 or 100 mu mol of Co(II) acetate/kg body wt in a single ip dose and killed 2 or 10 days later. Control rats received 200 mu mol of sodium acetate/k g body wt. Chromatin was isolated from organs and analyzed by gas chro matography/mass spectrometry with selected ion monitoring. The followi ng II products derived from purine and pyrimidine bases in DNA were qu antified: 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin, 5-(hydroxym ethyl)uracil (5-OHMe-Ura), 5-hydroxycytosine (5-OH-Cyt), thymine glyco l, 5,6-dihydroxycytosine, 4,6-diamino-5-formamido-pyrimidine pyAde),2, 6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), 7,8-dihyaro-8-oxo adenine,2-oxoadenine, and 7,8-dihydro-8-oxoguanine. The response was o rgan-specific. Eight of the DNA base products in renal chromatin of Co (II)-treated rats (mostly 5-OH-Cyt and other pyrimidine products), fiv e in hepatic chromatin (mostly FapyGua and other purine products), and two in pulmonary chromatin (5-OHMe-Ura > FapyAde) were increased by 3 0% to more than 200% over control levels with increasing Co(II) dose. The renal and hepatic, but not pulmonary, DNA base damage tended to in crease with time. No significant differences in response were found be tween male and female rats. The bases determined were typical products of hydroxyl radical attack on DNA, suggesting a role for this radical in the mechanism(s) of DNA damage caused by Co(II) in vivo. Some of t hese bases have been shown previously to be promutagenic. The present results imply involvement of oxidative DNA base damage in Co(II)-induc ed genotoxic and carcinogenic effects.