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血清双酚 A 药代动力学及新生 Sprague-Dawley 大鼠经口和皮下暴露后的前列腺肿瘤反应。

Serum bisphenol A pharmacokinetics and prostate neoplastic responses following oral and subcutaneous exposures in neonatal Sprague-Dawley rats.

机构信息

Department of Urology, 820 S Wood St, MC 955, University of Illinois at Chicago, Chicago, IL 60612, USA.

出版信息

Reprod Toxicol. 2011 Jan;31(1):1-9. doi: 10.1016/j.reprotox.2010.09.009. Epub 2010 Oct 8.

Abstract

The present study examines BPA pharmacokinetics in neonatal rats following s.c. injection or oral delivery of 10 μg BPA/kg BW and compares susceptibility to estrogen-induced prostate intraepithelial neoplasia (PIN) following either exposure route. Serum BPA in PND3 rats was measured using HPLC-MS-MS. Free and total BPA at C(max) were 1.77 and 2.0 ng/ml, respectively following injection and 0.26 and 1.02 ng/ml, respectively following oral exposure. The AUC(0-2) for free and total BPA was 4.1-fold and 1.8-fold greater, respectively, in s.c. vs. oral delivery. While exposure route affected BPA metabolism, internal dosimetry following s.c. injection of 10 μg BPA/kg BW is similar to BPA levels observed in humans. Prostates from aged rats given s.c. or oral BPA neonatally and T+E implants as adults exhibited nearly identical, heightened susceptibility to PIN incidence and score as compared to neonatal oil-controls. These findings on prostate health are directly relevant to humans at current BPA exposure levels.

摘要

本研究通过对新生大鼠皮下注射或口服 10μg BPA/kg BW 研究 BPA 的药代动力学,并比较了两种暴露途径下对雌激素诱导的前列腺上皮内瘤形成(PIN)的易感性。在 PND3 大鼠的血清中采用 HPLC-MS-MS 法测量 BPA。在注射和口服暴露后,C(max)时的游离和总 BPA 分别为 1.77 和 2.0ng/ml,0.26 和 1.02ng/ml。与口服相比,游离和总 BPA 的 AUC(0-2)分别增加了 4.1 倍和 1.8 倍。虽然暴露途径会影响 BPA 的代谢,但 10μg BPA/kg BW 皮下注射后的体内剂量与人类观察到的 BPA 水平相似。与新生期油对照相比,接受新生期皮下注射或口服 BPA 以及成年时 T+E 植入的老年大鼠的前列腺表现出几乎相同的、高度易发性 PIN 发生率和评分。这些关于前列腺健康的发现与当前 BPA 暴露水平下的人类直接相关。

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