Exposure-route-dependent DNA adduct formation by polycyclic aromatic hydrocarbons
Exposure-route-dependent DNA adduct formation by polycyclic aromatic hydrocarbons
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DOI：
10.1093/carcin/21.1.87
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发表时间：
2000-01-01
期刊：
影响因子：
4.7
通讯作者：
Van Schooten, FJ
中科院分区：
文献类型：
--
作者：
Godschalk, RWL;Moonen, EJC;Van Schooten, FJ
了解靶组织和白色血细胞（WBC）中芳香族DNA加合物的动力学将增强WBC中DNA加合物作为DNA替代来源在生物监测研究中的适用性。在本研究中，大鼠急性暴露于苯并[a]芘（B[a]P; 10 mg/kg体重），皮肤和口服给药。在暴露后1、2、4、11和21天，通过富含核酸酶P1的P-32后标记分析相关靶器官和WBC中的DNA加合物。此外，通过测量3-羟基-B [a]P（3-OH-B[a]P）的尿排泄来评估内部剂量。和口服给药，而DNA加合物在皮肤暴露后几乎检测不到。在接触后2天达到最高加合物水平。在肺组织中，DNA加合物水平在第2天达到最大值，并且在i.t.后最高，经口和皮肤接触。与肺相比，WBC中的DNA加合物水平显著较低。尽管如此，WBC中的总体B[a]P-DNA加合物水平与肺中的水平显著相关。在靶器官中，局部应用后在皮肤中观察到最高的DNA加合物水平，口服B[a]P后在胃中观察到最低的DNA加合物水平。此外，WBC中的DNA加合物水平与皮肤暴露后皮肤中的DNA加合物水平相关，口服B[a]P后胃中的DNA加合物水平相关，i.t.后排泄的3-OH-B[a]P水平高出两倍与皮肤或口服暴露相比，施用B[a]P，尿3-OH-B[a]P浓度与施用B[a]P部位的DNA加合物水平相关。总体而言，可以得出结论，WBC中的芳香族DNA加合物水平可用作B[a]P应用部位的DNA替代来源，并反映与肺DNA的结合，与暴露途径无关。
Understanding the kinetics of aromatic-DNA adducts in target tissues and white blood cells (WBC) would enhance the applicability of DNA adducts in WBC as surrogate source of DNA in biomonitoring studies. In the present study, rats were acutely exposed to benzo[a]pyrene (B[a]P; 10 mg/kg body wt) via intratracheal (i.t.), dermal and oral administration. DNA adducts were analyzed in relevant target organs and WBC by nuclease P1 enriched P-32-post-labeling at 1, 2, 4, 11 and 21 days after exposure. Additionally, the internal dose was assessed by measurement of urinary excretion of 3-hydroxy-B[a]P (3-OH-B[a]P), Total B[a]P-DNA adduct levels in WBC were highest after i.t. and oral administration, whereas DNA adducts were hardly detectable after dermal exposure. Highest adduct levels were reached at 2 days after exposure. In lung tissue, DNA adduct levels reached maximal values at 2 days and were highest after i.t., oral and dermal exposure, respectively. DNA adduct levels were significantly lower in WBC as compared with lung. Nonetheless, overall B[a]P-DNA adduct levels in WBC were significantly correlated with those in lung. In target organs, highest DNA adduct levels were observed in skin after topical application, and lowest in stomach after oral administration of B[a]P, Furthermore, DNA adduct levels in WBC were correlated with DNA adduct levels in skin after dermal exposure and stomach after oral administration of B[a]P, Two-fold higher levels of 3-OH-B[a]P were excreted after i.t. administration of B[a]P as compared with dermal or oral exposure, Urinary 3-OH-B[a]P concentrations were correlated with DNA adduct levels at the site of B[a]P application. Overall, it can be concluded that aromatic-DNA adduct levels in WBC can be applied as a surrogate source of DNA for the site of application of B[a]P and reflect binding to lung DNA, independently of the exposure route.