Fedtke N, Boucheron J A, Walker V E, Swenberg J A
Chemical Industry Institute of Toxicology, Department of Biochemical Toxicology and Pathology, Research Triangle Park, NC 27709.
Carcinogenesis. 1990 Aug;11(8):1287-92. doi: 10.1093/carcin/11.8.1287.
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.
研究了暴露于氯乙烯（VC）的断乳前Sprague-Dawley大鼠体内DNA加合物7-(2'-氧代乙基)鸟嘌呤（OEG）和N2,3-乙烯基鸟嘌呤（EG）的形成和持久性。将带有10日龄幼崽的哺乳期雌性CD大鼠通过吸入600 ppm的VC，每天4小时，持续5天。在暴露后立即以及暴露后3天、7天和14天处死大鼠组。测定肝脏、肺、肾、脑和脾脏中OEG和EG的浓度。采用带荧光检测的高效液相色谱法检测OEG，采用气相色谱-负离子化学电离质谱法检测EG。在新生大鼠的组织中，以每微摩尔未修饰鸟嘌呤中pmol数表示的两种DNA加合物浓度在肝脏中最高（OEG 162±36，EG 1.81±o.25），其次是肾脏（OEG 29±1，EG 0.31±0.02）和肺（OEG 20±7，EG 0.21±0.08）。在脑或脾脏中未发现加合物。仅在母鼠的肝脏（OEG 43±7，EG 0.47±0.14）和肺（OEG 20±5，EG 0.27±0.03）中检测到DNA加合物。暴露后立即在所有组织中，EG与OEG的比例约为1:100。在断乳前大鼠的肝脏中，该比例在暴露1周后增加到1:14，反映出EG的持久性更强。计算出OEG的半衰期为62小时，EG的估计半衰期大于30天。鉴于EG的缓慢消除及其导致碱基对错配的高效率，这些结果表明EG可能是VC诱导致癌过程中的一种重要DNA加合物。
