MOLECULAR BIOMARKERS

该计划的总体目标是改进和验证 人体暴露于芳香族和杂环化合物的分子生物标志物 胺，并利用这些标记来确定杂环的作用 胺对结肠癌的风险和芳香胺对结肠癌的风险 不同人种和民族吸烟者与非吸烟者膀胱癌的研究 组。在洛杉矶，这些人将包括拉丁裔、非裔美国人， 日本人和白人；确定的队列也将在新加坡进行研究， 中国和日本。在项目I中，血红蛋白加合物将用于 还要确定人体接触N-羟基烷基苯胺的程度 作为调节其活性的关键酶。尿代谢物 排泄物将被用来确定代谢多态和暴露 不同种族和民族对特定杂环胺的反应，以及 在以下情况下也要确定暴露与结肠癌的关系- 对照研究。在项目2中，杂环胺的测量方法- 尿液和细胞DNA中的DNA加合物将被开发和验证为 生物有效暴露的标志物。这些标记将被用来 确定DNA加合物的形成与结肠癌风险的关系 癌症的病例对照研究和评估不同种族的暴露 和种族群体。测定4-脱氧核糖核酸主要DNA加合物的方法学 尿液和细胞DNA中的氨基联苯将被开发并用于 确定DNA加合物的形成与膀胱癌风险的关系 一项病例对照研究中的癌症。此外，还将制定方法论 用于测量细胞DNA中的总DNA加合物水平，以便 评估不同致癌物暴露之间可能的相互作用。项目 3将确定接触杂环胺的流行率和 不同种族和民族之间的烷基苯胺，并确定 接触这些物质的饮食和其他可能的环境因素 种族群体内部和群体之间的化合物。另外， 将进行初步研究，以调查两者之间的关系 暴露于杂环胺和结直肠癌，以及在 芳胺和烷基苯胺暴露与膀胱癌。相互关系 不同生物标记物之间以及目标组织水平之间， 以及与酶基因型别/表型的关系 还将对种族/民族之间的关系进行调查。团结在一起， 个别项目将提供补充数据，以评估 分子生物标记物在生物效应测量中的有效性 暴露，并检验暴露于芳香族和 杂环胺增加膀胱、结肠和胰腺的风险 癌症。

The overall objectives of this program are to refine and validate molecular biomarkers of human exposures to aromatic and heterocyclic amines, and to utilize the markers to determine the roles of heterocyclic amines on the risk of colon cancer and aromatic amines on the risk of bladder cancer in smokers and nonsmokers in different racial and ethnic groups. In Los Angeles, these will include Latinos, African Americans, Japanese and Whites; defined cohorts will also be studied in Singapore, China and Japan. In Project I, hemoglobin adducts will be used to determine the extent of human exposure to N.hydroxyalkylanilines, as well as the key enzymes regulating their activation. Urinary metabolite excretion will be used to determine metabolic polymorphisms and exposure of different racial and ethnic groups to specific heterocyclic amines, and also determine the relationship between exposure and colon cancer in case- control studies. In project 2, methods for measuring heterocyclic amine- DNA adducts in urine and cellular DNA will be developed and validated as markers of biologically effective exposures. The markers will be used to determine relationships between DNA adduct formation and risk of colon cancer in case control studies and to assess exposure in different racial and ethnic groups. Methodology for measuring the major DNA adduct of 4- aminobiphenyl in urine and cellular DNA will be developed and used to determine relationships between DNA adduct formation and risk of bladder cancer in a case-control study. In addition, methodology will be developed for measurement of total DNA adduct levels in cellular DNA in order to assess possible interactions among diverse carcinogen exposures. Project 3 will determine prevalence of exposure to heterocyclic amines and alkylanilines among different racial and ethnic groups, and also determine dietary and other possible environmental correlates of exposure to these compounds within and between racial-ethnic groups. Additionally, preliminary studies will be conducted to investigate relationships between exposure to heterocyclic amines and colorectal cancer, and between arylamine and alkylaniline exposure and bladder cancer. Interrelationships between different biomarkers and each other and to target tissue levels, as well as relationships to enzymatic genotypes/phenotypes within and between racial/ethnic groups will also be investigated. Together, the individual projects will provide complementary data for assessing the validity of molecular biomarkers in measuring biologically effective exposures, and testing the hypothesis that exposure to aromatic and heterocyclic amines increases risk for bladder and colon and pancreatic cancers.