ARACHIDONIC ACID METABOLISM AND CANCER CHEMOPREVENTION

乳腺癌仍然是癌症发病率和死亡率的主要原因 年龄在15到74岁之间的美国女性。 因此，除了传统 治疗方式，预防乳腺癌的新策略， 这是为了控制疾病。 这些战略， 寻求在肿瘤前期抑制乳腺癌诱导， 可以有多种机制基础，包括差异生物学 正常细胞和肿瘤细胞。 花生四烯酸代谢增加 在许多肿瘤组织中，包括实验和人类乳腺 癌 结果，几种花生四烯酸代谢物的水平 与正常人相比， 乳腺 花生四烯酸代谢的调节 前列腺素合成酶抑制剂吲哚美辛和氟比洛芬结果 在显著抑制大鼠乳腺癌的诱导中， 一种化学致癌物 然而，由于前列腺素的抑制 合成酶抑制许多类花生酸的产生， 花生四烯酸代谢在肿瘤发生中的特定途径， 未知 为了解决这个问题，提出了研究，其中抑制剂 花生四烯酸级联反应中的特定酶将被施用， 大鼠先前暴露于乳腺致癌物N-甲基-N-亚硝基脲。 这些药物对乳腺癌发病率、肿瘤大小、 将确定多重性和肿瘤潜伏期，以评估其疗效 作为致癌抑制剂。 此外， 将检查膳食脂肪对这种抑制作用的影响。 在这种情况下，角色 乳腺癌中花生四烯酸代谢的特定途径 可以确定致癌作用，以及调节致癌作用的效用。 可以探索类二十烷酸生物合成作为癌症预防的途径。

Breast cancer remains the leading cause of cancer morbidity and mortality in American women aged 15 to 74 years. Thus, in addition to traditional therapeutic modalities, new strategies for breast cancer prevention are called for in the attempt to control the disease. These strategies, which seek to inhibit breast cancer induction during the preneoplastic period, can have a variety of mechanistic bases, including the differential biology of normal and neoplastic cells. Arachidonic acid metabolism is increased in many neoplastic tissues, including experimental and human mammary carcinomas. As a result, levels of several arachidonic acid metabolites (eicosanoids) are increased in mammary cancers as compared to normal mammary gland. Modulation of arachidonic acid metabolism with the prostaglandin synthetase inhibitors indomethacin and flurbiprofen results in a significant inhibition of mammary cancer induction in rats exposed to a chemical carcinogen. However, since inhibition of prostaglandin synthetase inhibits the production of many eicosanoids, the role of specific pathways of arachidonic acid metabolism in carcinogenesis is unknown. To address this issue, studies are proposed in which inhibitors of specific enzymes in the arachidonic acid cascade will be administered to rats previously exposed to the mammary carcinogen N-methyl-N-nitrosourea. The effects of these agents on mammary cancer incidence, tumor multiplicity, and tumor latency will be determined to assess their efficacy as inhibitors of carcinogenesis. Furthermore, the modifying effect of dietary fat on this inhibition will be examined. In this manner, the role of specific pathways of arachidonic acid metabolism in mammary carcinogenesis can be determined, and the utility of modulation of eicosanoid biosynthesis as an avenue for cancer prevention can be explored.