Modulation of adult rat benzo(a)pyrene (BaP) metabolism and DNA adduct formation by neonatal diethylstilbestrol (DES) exposure
Modulation of adult rat benzo(a)pyrene (BaP) metabolism and DNA adduct formation by neonatal diethylstilbestrol (DES) exposure
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DOI：
10.1016/j.etp.2004.08.005
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Knuckles, ME
中科院分区：
文献类型：
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作者：
Ramesh, A;Inyang, F;Knuckles, ME
本研究旨在阐明己烯雌酚（DES）（一种合成雌激素）对雄性大鼠生殖组织中苯并（a）芘（BaP）代谢的作用。定时妊娠 Sprague-Dawley 大鼠的后代在产后第 2、4 和 6 天用 1.45 mumol/kg DES 进行新生儿治疗。出生10周后，用放射性标记的苯并(a)芘(H-3 BaP)(10μmol/kg)攻击成年大鼠，并在BaP暴露后2It处死大鼠。俯伏。睾丸。肺。肝。收集尿液和粪便样本，并使用 H2O、MeOH 和 CHCl3 的混合物提取。通过反相 HPLC 分析提取物。与对照组（媒介物处理的大鼠）相比，DES 大鼠中 BaP 有机代谢物的浓度较低。另一方面，DES 处理的动物中水性代谢物的浓度显着增加。与对照组相比，DES 大鼠的中毒与解毒比率显着降低。这一趋势也反映在 DES 大鼠中 BaP-DNA 加合物浓度的降低。总的来说，这些结果表明 DES 能够调节 BaP 的解毒代谢途径，从而防止毒性的表现。 (C) 2004 年爱思唯尔有限公司。版权所有。
This study seeks to elucidate the role of diethylstilbestrol (DES), a synthetic estrogen on benzo(a)pyrene (BaP) metabolism in the male rat reproductive tissues. Offspring of timed-pregnant Sprague-Dawley rats were neonatally treated on days 2, 4, and 6 post-partum with 1.45 mumol/kg of DES. Ten weeks after birth, the adult rats were challenged with radiolabeled benzo(a)pyrene (H-3 BaP) (10 mumol/kg) and the rats were sacrificed 2 It after BaP exposure. Prostrate. testis. lung. liver. urine and feces samples were collected and extracted using a mixture of H2O, MeOH and CHCl3. The extracts were analyzed by reverse phase HPLC. The concentrations of BaP organic metabolites in DES rats were lower compared to controls (vehicle-treated rats). On the other hand, concentrations of aqueous metabolites were significantly increased in DES treated animals. The toxication to detoxication ratios were significantly decreased in DES rats compared to controls. This trend is also reflected in the decreased concentrations of BaP-DNA adducts in DES rats. Collectively these results suggest that DES is capable of modulating the metabolic pathway of BaP towards detoxification thereby preventing the manifestation of toxicity. (C) 2004 Elsevier GmbH. All rights reserved.