MOLECULAR BIOMARKERS

该计划的总体目标是完善和验证 人类暴露于芳香族和杂环的分子生物标志物 胺，并利用标记物来确定杂环的作用 胺对结肠癌的风险和芳香胺的风险 不同种族和民族中吸烟者和非吸烟者的膀胱癌 组在洛杉矶，这些将包括拉丁美洲人，非洲裔美国人， 日本人和白人;还将在新加坡研究规定的队列， 中日两国在项目I中，血红蛋白加合物将用于 确定人类暴露于N.羟烷基苯胺的程度，以及 作为调节其活化的关键酶。尿代谢物 排泄将用于确定代谢多态性和暴露 不同种族和民族群体对特定杂环胺的敏感性， 也确定暴露与结肠癌之间的关系， 对照研究。在项目2中，测量杂环胺的方法- 将开发并验证尿液和细胞DNA中的DNA加合物， 生物有效暴露的标志物。这些标记将用于 确定DNA加合物形成与结肠癌风险之间的关系 癌症病例对照研究，并评估不同种族 和种族群体。用于测量4-甲基-N-（2-甲基-N-苯基）-2-氧代-N-氧代）的主要DNA加合物的方法学 尿和细胞DNA中的氨基联苯将被开发并用于 确定DNA加合物形成与膀胱癌风险之间的关系 癌症病例对照研究。此外，还将制定方法 用于测量细胞DNA中的总DNA加合物水平， 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患病率， 烷基苯胺在不同的种族和民族群体，也决定了 饮食和其他可能的环境相关因素 种族内部和种族之间的化合物。此外，本发明还 将进行初步研究，以调查 暴露于杂环胺和结直肠癌，以及 芳胺和烷基苯胺暴露和膀胱癌。相互关系 不同生物标志物之间的相互作用以及靶组织水平， 以及与酶基因型/表型的关系， 还将调查种族/族裔群体之间的关系。统称 个别项目将提供补充数据， 分子生物标志物在测量生物有效性中的有效性 暴露，并测试假设，暴露于芳香和 杂环胺增加膀胱、结肠和胰腺癌的风险 癌的

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.