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首页> 外文学位 >Benzo(a)pyrene and benzo(a)pyrene-induced protein adducts in hair as biomarkers of toxic benzo(a)pyrene exposures.
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Benzo(a)pyrene and benzo(a)pyrene-induced protein adducts in hair as biomarkers of toxic benzo(a)pyrene exposures.

机译：苯并（a）and和苯并（a）-诱导的头发蛋白质加合物是有毒苯并（a）exposure暴露的生物标志物。

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摘要

Cigarette smoking is the leading cause of preventable death in the United States. While there are more than 4,000 chemicals found in tobacco smoke, the polycyclic aromatic hydrocarbons (PAHs) have been clearly demonstrated to contribute to smoking-related cancers. Of this group of compounds, benzo(a)pyrene (B(a)P) is considered to be the most carcinogenic and its ability to cause lung tumors is well documented.;Many conventional biomarker assays conducted today use the measurement of nicotine (and its metabolite cotinine) in blood, urine, or oral fluids for assessment of tobacco smoke exposure. However, these conventional assays do not measure exposure to carcinogenic compounds and are sensitive only to recent smoke exposures. Due to the ease of hair sampling and its extended detection window of substances incorporated into its matrix, this dissertational research proposes a promising new tool for the assessment of toxic tobacco smoke exposure.;We investigated the disposition of B(a)P and its electrophilic reactive metabolite, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-benzo(a)pyrene (BPDE), in rat and human hair. BPDE is one of the most potent mutagens and carcinogens known, and forms protein and DNA adducts in multiple tissues. Our overarching hypothesis was that B(a)P and BPDE-protein adducts in hair can be used as biomarkers of toxic B(a)P exposure.;The data presented in this dissertation demonstrate that B(a)P and BPDE-protein adducts are incorporated into rat hair in a dose-dependent manner. While B(a)P incorporation into rat hair is not dependent upon pigment content, BPDE-protein adducts concentrations are significantly greater in pigmented vs. nonpigmented hair.;Gross histopathological changes in rat lung tissue, such as alveolar wall thickening, decreased air space, and macrophage hyperplasia were visually evident in rats 14 days after B(a)P administration. Immunohistochemistry staining for myeloperoxide content (a marker for neutrophils) in the lung tissue of B(a)P-dosed rats was also significantly greater than vehicle control rats.;B(a)P can be detected in human hair, but BPDE-protein adducts could not be detected, despite evidence of active smoking status via plasma cotinine concentrations.;The results of this dissertational research demonstrate that hair may serve as an easily accessible surrogate tissue for the detection of a biomarker of toxic tobacco smoke exposure.
机译：在美国，吸烟是可预防的死亡的主要原因。尽管在烟草烟雾中发现了4000多种化学物质，但多环芳烃（PAHs）已明确证明可导致与吸烟有关的癌症。在这组化合物中，苯并（a）（（B（a）P）被认为是最致癌的，其引起肺部肿瘤的能力已得到充分证明。今天进行的许多常规生物标志物测定均使用尼古丁（和血液，尿液或口服液中的代谢产物可替宁），以评估烟草烟雾暴露。然而，这些常规测定不能测量致癌化合物的暴露，仅对最近的烟雾暴露敏感。由于头发采样的简便性以及其基质中所含物质的扩展检测窗口，本论文研究提出了一种有前途的新工具，用于评估有毒烟草烟雾的暴露。；我们研究了B（a）P及其亲电子的处置大鼠和人头发中的反应性代谢产物，反式7,8-二羟基-抗-9,10-环氧-7,8,9,10-四氢-苯并（a）（（BPDE）。 BPDE是已知的最有效的诱变剂和致癌物之一，可在多种组织中形成蛋白质和DNA加合物。我们的总体假设是，头发中的B（a）P和BPDE-蛋白质加合物可以用作毒性B（a）P暴露的生物标志物。本论文中的数据表明B（a）P和BPDE-蛋白质加合物以剂量依赖的方式将它们掺入大鼠毛发中。虽然将B（a）P掺入大鼠毛发并不取决于色素的含量，但是有色与无色素的毛发中BPDE-蛋白质加合物的浓度明显更高;;大鼠肺组织的严重组织病理学变化，例如肺泡壁增厚，气隙减少B（a）P给药后14天，大鼠肉眼可见巨噬细胞增生。用B（a）P给药的大鼠肺组织中的过氧化物含量（嗜中性粒细胞的标志物）的免疫组织化学染色也显着高于溶媒对照大鼠。;在人的头发中可以检测到B（a）P，但是BPDE蛋白尽管通过血浆可替宁浓度证明有活跃的吸烟状态，但仍未检测到加合物。这项论文的研究结果表明，毛发可以作为容易接触的替代组织，用于检测有毒烟草烟雾暴露的生物标记。

著录项

  • 作者

    Campbell, Sarah Colleen.;

  • 作者单位

    The University of Utah.;

  • 授予单位 The University of Utah.;
  • 学科 Health Sciences Toxicology.;Health Sciences Pharmacology.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 200 p.
  • 总页数 200
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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