Dose-dependent benzo(a)pyrene [B(a)P]-DNA adduct levels and persistence in F-344 rats following subchronic dietary exposure to B(a)P.
Dose-dependent benzo(a)pyrene [B(a)P]-DNA adduct levels and persistence in F-344 rats following subchronic dietary exposure to B(a)P.
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DOI：
10.1016/j.canlet.2005.09.016
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发表时间：
2006-08
期刊：
影响因子：
9.7
通讯作者：
A. Ramesh;M. E. Knuckles
中科院分区：
文献类型：
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作者：
A. Ramesh;M. E. Knuckles
为了探讨BaP - DNA加合物的形成与长期暴露于苯并(a)芘（BaP）之间的关系，测定了亚慢性暴露于BaP的雄性和雌性F-344大鼠肝脏和肺组织中DNA加合物的水平。在90天的时间里，分别在动物饲料中添加0、5、50和100mg/kg BaP，分别代表对照、低剂量、中剂量和高剂量。给药后，处死动物，切除肝脏和肺组织，分离DNA，采用四向薄层色谱系统32p后标记法分析bap诱导的DNA加合物。在低剂量和中等剂量的BaP下，组织中的DNA加合物水平与暴露显著相关。然而，在高BaP剂量下，剂量- dna加合物关系变为非线性关系。同样，中剂量和高剂量下的相对DNA加合物持久性显著高于低剂量下的测量值。低、中剂量线性和高剂量非线性可能是由于代谢激活和解毒酶的饱和以及DNA修复过程。
In order to investigate the relationship between BaP–DNA adduct formation and long-term exposure to benzo(a)pyrene (BaP), DNA adduct levels in liver and lung tissues of male and female F-344 rats subchronically exposed to BaP were determined. Doses of 0, 5, 50, and 100mg/kg BaP, representing control, low, intermediate, and high doses, respectively, were administered in the animal diet over a 90-day period. After dosing, animals were sacrificed, liver and lung tissues were removed, DNA was isolated and analyzed for BaP-induced DNA adducts by the32P-postlabeling method using a four-directional thin-layer chromatography system. At low and intermediate BaP doses, DNA adduct levels in the tissues were significantly correlated with exposure. However, at high BaP doses, the dose-DNA adduct relationship became non-linear. Similarly, the relative DNA adducts persistence at intermediate and high doses were significantly higher than that measured at low dose. The low and intermediate dose linearity and high dose non-linearity may be due to saturation of metabolic activation and detoxification enzymes, and DNA repair processes.