CANCER CAUSE & PREVENTION RESEARCH

该研究计划的总体目标是提供新的 这些信息将增加我们对癌症病因的理解， 为预防癌症提供了新的方法。 拟议研究 涉及： (1)近因和最终致突变性和致癌性鉴定 多环芳烃和相关氮的代谢物， 含有杂环化合物。 的另一主要目的 这项研究是为了加强我们对探索不足的方面的理解， 多环芳烃二醇环氧化物构效关系 碳氢化合物和含氮杂细胞。 (2)光学活性R，S， 多环芳烃的S，R湾区二醇环氧化物，和 含氮杂环。 在本研究中，我们将使用R，S，S，R 海湾地区二醇环氧化物（最终诱变剂和致癌物）及其 近缘光学活性但生物活性较低或无活性 S，R，R，S对映体， 作为鉴定细胞靶的探针的含氮杂环 对诱变很重要。 我们将确定（a）的影响 DNA碱基序列上的光学活性湾区二醇环氧化物对映体 在内源性次黄嘌呤的编码区 中国仓鼠V-79细胞的磷酸核糖基转移酶基因和（B） 光学活性湾区二醇环氧化物对映体对 DNA聚合酶的保真度（a）最终的可能蛋白质靶点 致癌物）。 (3)天然存在的膳食成分的抑制作用， 其衍生物对化学致癌作用和紫外线诱导的 致癌作用 在这项研究中，我们将尝试识别潜在的 有用的致癌抑制剂，并将这些抑制剂用作工具， 以更好地了解致癌过程。 我们将评估（a） 多环芳族的海湾区二醇环氧化物的潜在拮抗剂 芳香烃. (b)姜黄素，鼠尾草酚， 迷迭香和其他膳食植物物质对化学致癌作用的影响， 紫外线诱导的致癌作用和（c）潜在的抑制作用 和/或维生素D3、1 α，25-二羟基维生素D3和 钙对化学致癌和紫外线诱发的 致癌作用 将对可能的作用机制进行评价。

The overall objective of the proposed research program is to provide new information that will increase our understanding of cancer causation and provide new approaches for the prevention of cancer. The proposed research is concerned with: (1) identification of proximate and ultimate mutagenic and carcinogenic metabolites of polycyclic aromatic hydrocarbons and related nitrogen- containing heterocyclic compounds in our environment. An important aim of this research is to enhance our understanding of poorly explored aspects of structure-activity relationships of diol epoxides from polycyclic aromatic hydrocarbons and nitrogen-containing heterocytes. (2) mechanisms of carcinogenesis and mutagenesis by optically active R, S, S, R bay-region diol epoxides of polycyclic aromatic hydrocarbons and nitrogen-containing heterocycles. In this research, we will use R, S, S, R bay-region diol epoxides (ultimate mutagens and carcinogens) and their closely related optically active but biologically less active or inactive S, R, R, S enantiomers from several polycyclic aromatic hydrocarbons and nitrogen-containing heterocycles as probes for identifying cellular targets that are important for mutagenesis. We will determine (a) the effect of optically active bay-region diol epoxide enantiomers on DNA base sequences in the coding region of the endogenous hypoxanthine phosphoribosyltransferase gene of Chinese hamster V-79 cells and (b) effects of optically active bay-region diol epoxide enantiomers on the fidelity of DNA polymerase (a) possible protein target for ultimate carcinogens). (3) inhibitory effects of naturally occurring dietary constituents and their derivatives on chemical carcinogenesis and ultraviolet light-induced carcinogenesis. In this research, we will attempt to identify potentially useful inhibitors of carcinogenesis and to use these inhibitors as tools for better understanding of the carcinogenic process. We will evaluate (a) potential antagonists of bay-region diol epoxides of polycyclic aromatic hydrocarbons. (b) potential inhibitory effects of curcumin, carnosol, rosemary and other dietary plant substances on chemical carcinogenesis and ultraviolet light-induced carcinogenesis and (c) potential inhibitory and/or stimulatory effects of vitamin D3, 1alpha,25-dihydroxyvitamin D3 and calcium on chemical carcinogenesis and ultraviolet light-induced carcinogenesis. Possible mechanisms of action will be evaluated.