MOLECULAR BIOMARKERS OF OCCUPATIONAL BENZENE EXPOSURE

增加对DNA和染色体易感性的遗传特征 活性环氧化物和过氧化氢的损害可能是重要的个人风险 人类癌症发展的因素。在本研究中，我们将 猪谷胱甘肽S转移酶家族的基因多态性研究 酶作为致癌物暴露易感性的潜在标记。这个 这些研究的特别重点是深入探讨 一种新发现的GSTT1基因缺失多态及其生物标志物 暴露、早期生物效应和癌症发生--特别是 儿童白血病和膀胱癌。因为流行性感冒的流行 GSTT1缺失在不同的人群中是未知的，重要的是 获取该性状在不同民族中分布的背景数据 和种族团体。我们将比较GSTT1缺失的发生率 在不同的种族和种族群体中使用基于PCR的分析 包括：高加索人、中国人、韩国人、非裔美国人和墨西哥人，以及 墨西哥西班牙裔受试者。接下来，将进行研究，以研究 GSTT1基因多态性作为遗传毒性生物标志物修饰物的作用 与内源性和环境暴露有关。体外研究 将进行测试，以测试GSTT1缺陷的个体是否 对脂质引起的染色体损伤和DNA加合物过敏 过氧化氢，可能来自饮食或暴露于 卤代烃。此外，由于可能参与其中， 受氯代烃污染的饮用水与膀胱癌 和白血病，我们将测试GSTT1缺失对 三卤代甲烷。因为GSTT1与 姐妹染色单体交换频率及其与饮食相关的解毒作用 脂肪酸氢过氧化，我们将考察饮食的潜在作用 并将姐妹染色单体交换数据与血脂水平相关联 过氧化氢DNA加合物。检查癌症风险的潜在修饰 我们将对GSTM1的患病率进行病例对照比较 儿童白血病GSTT1缺失与GSTT1状态的相关性 膀胱癌中P53基因的突变谱。突变 数据和基因分型数据将与正在进行的流行病学调查合并 评估GDT多态可能与 儿童白血病和膀胱的饮食和环境危险因素 癌症。

Genetic traits that confer increased susceptibility to DNA and chromosomal damage by reactive epoxide and peroxides could be important individual risk factors in the development of human cancers. In the present study we will focus on polymorphisms within the glutathione S-transferase (GST) family of enzymes as potential markers of susceptibility to carcinogen exposure. The special focus of these studies is to explore in depth the relationship of a newly discovered deletion polymorphism in GSTT1 with biomarkers of exposure, early biologic effect, and cancer occurrence--specifically childhood leukemia, and bladder cancer. Because the prevalence of the GSTT1 deletion is unknown in different populations, it is important to obtain background data on the distribution of the trait in different ethnic and racial groups. We will compare the prevalence of the GSTT1 deletion using a PCR based assay in various ethnic and racial groups including:Caucasian, Chinese, korean, African-American, and mexican, and Mexican Hispanic subjects. Next, studies will be undertaken to examine the role of the GSTT1 polymorphism as a modifier of biomarkers of genotoxicity associated with endogenous and environmental exposures. In vitro studies will be undertaken o test whether individuals deficient in GSTT1 are hypersensitive to chromosomal damage and DNA adducts induced by lipid hydroperoxides, which may be derived from the diet or through exposure to halogenated hydrocarbons. In addition, because of the possible involvement of chlorinated hydrocarbons contaminated drinking water and bladder cancer and leukemia, we will test the effects of GSTT1 deletion on trihalomethanes. Because GSTT1 is associated with background variations in SCE frequencies and is implicated in the detoxification of diet-related fatty acid hydroperoxides, we will examine the potential role of diet on the SCE marker and will correlate the SCE data with the levels of lipid peroxide DNA adducts. To examine the potential modification of cancer risk we will carry out case-control comparisons of the prevalence of the GSTM1 and GSTT1 deletion in childhood leukemia and correlate GSTT1 status with the mutational spectra within the p53 gene in bladder tumors. Mutation data and genotyping data will be merged with the ongoing epidemiologic projects to assess the possible relationships of GDT polymorphisms with dietary and environmental risk factors for childhood leukemia and bladder cancer.