CANCER CAUSE & PREVENTION RESEARCH

拟议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和 为预防癌症提供新的方法。拟议的研究 关注的是： (1)近致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- 在我们的环境中含有杂环化合物。的一个重要目标 这项研究是为了加强我们对未被探索的方面的了解 多环芳烃二醇环氧化物的构效关系 碳氢化合物和含氮杂细胞。 (2)光学活性R的致癌和致突变机制，S， S，R湾区多环芳烃二醇环氧化物和 含氮杂环。在本研究中，我们将使用R、S、S、R 湾区二元醇环氧化物(终极致突变物和致癌物)及其 密切相关的光学活性，但生物学上不太活跃或不活跃 几种多环芳烃的S、R、R、S对映体 含氮杂环作为识别细胞靶标的探针 对突变很重要的基因。我们将确定(A)影响 DNA碱基序列上具有光学活性的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细胞的磷酸核糖转移酶基因和(B) 光学活性湾区二醇环氧化物对映体的影响 DNA聚合酶的保真度(A)可能成为终极目标的蛋白质 致癌物质)。 (3)天然饮食成分的抑制作用 其衍生物对化学致癌和紫外光诱导的影响 致癌。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 以便更好地了解致癌过程。我们将评估(A) 多环芳香族湾区二醇环氧化物的潜在拮抗剂 碳氢化合物。(B)姜黄素、卡诺醇、 迷迭香和其他膳食植物物质对化学致癌和 紫外光致癌和(C)电位抑制 和/或维生素D3、1α、25-二羟基维生素D3和 钙在化学致癌和紫外线诱导中的作用 致癌。将对可能的行动机制进行评估。

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.