Vinyl chloride-induced DNA adducts. II: Formation and persistence of 7-(2'-oxoethyl)guanine and N2,3-ethenoguanine in rat tissue DNA.
The formation and persistence of the DNA adducts 7-(2'-oxoethyl)guanine (OEG) and N2,3-ethenoguanine (EG) were investigated in preweanling Sprague-Dawley rats exposed to vinyl chloride (VC). Lactating female CD rats with 10 day old pups were exposed to 600 p.p.m. VC by inhalation for 5 days, 4 h/day. Groups of rats were killed immediately and 3, 7 and 14 days after exposure. The concentrations of OEG and EG were measured in liver, lung, kidney, brain and spleen. HPLC with fluorescence detection was used for OEG detection, and gas chromatography-negative ion chemical ionization mass spectrometry was used for EG detection. In tissues of neonatal rats, the concentrations of both DNA adducts, expressed as pmol/mumols unmodified guanine, were highest in liver (OEG 162 +/- 36, EG 1.81 +/- 0.25), followed by kidney (OEG 29 +/- 1, EG 0.31 +/- 0.02), and lung (OEG 20 +/- 7, EG 0.21 +/- 0.08). No adducts were found in brain or spleen. DNA adducts were detected only in liver (OEG 43 +/- 7, EG 0.47 +/- 0.14) and lung (OEG 20 +/- 5, EG 0.27 +/- 0.03) of the dams. The ratio between EG and OEG was approximately 1:100 in all tissues immediately after exposure. In the liver of the preweanling rats, this ratio increased to 1:14 1 week after exposure, reflecting a greater persistence of EG. A half-life of 62 h was calculated for OEG, and the estimated half-life for EG was greater than 30 days. In view of the slow loss of EG and its high efficiency for causing base-pair mismatch, these results suggest that EG may be an important DNA adduct in VC-induced carcinogenesis.
Fedtke
N
N
Chemical Industry Institute of Toxicology, Department of Biochemical Toxicology and Pathology, Research Triangle Park, NC 27709.
Boucheron
J A
JA
Walker
V E
VE
Swenberg
J A
JA
D000818:Animals; D004247:DNA / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014752:Vinyl Chloride / Q000378:metabolism* / Q000633:toxicity; D014753:Vinyl Compounds / Q000378:metabolism*
D014753:Vinyl Compounds; D006147:Guanine; C032220:7-N-(2-oxoethyl)guanine; D004247:DNA; D014752:Vinyl Chloride