CARCINOGENICITY OF FECAPENTAENES

人类排泄物被发现含有一组高度诱变的化合物 被称为肥五烯。这些化合物会产生多种遗传毒性物质 效果。它们是直接作用的诱变剂，增加大鼠的DNA合成 肝细胞，诱导小鼠BALB/c3T3细胞的肿瘤转化和 导致DNA单链断裂，姐妹染色单体交换和突变 人类成纤维细胞。上述研究结果表明， 人类大肠癌的病因可能已经找到了。 然而，到目前为止，一个成功的例子证明了由菲五烯诱导的 体内致癌还没有完成。存在的主要问题 可以解释这些负面结果的是有缺陷的处理 非常不稳定的菲五烯类化合物；不适当的溶剂； 以及不足的动物模型。当前的首要目标 一项建议是确定三氯甲烷是否能产生全部或部分 实验性大肠黏膜的肿瘤反应 动物。防止腐烂遗嘱分解的方法 被雇佣。将使用短期体内测试系统来确定 溶剂、给药条件和给药时间表最有可能导致 致癌反应。这些措施包括对扩建的评估 大肠隐窝增生室的测定 有丝分裂活性增加的存在，形成的研究 核异常，以及异常隐窝形成的研究。 采用由上述确定的最佳条件，致癌 将进行研究以确定费拉帕坦：(1)是不是完整的 致癌物，(2)是致癌物质，(3)是促癌物质，(4)可以 导致肿瘤进展，和/或(5)在 大肠粘膜。如果取得了积极的结果，他们可能 形成评估非均五烯类化合物致癌危害的基础 它的预防手段。

Human feces has been found to contain a group of highly mutagenic compounds called fecapentaenes. These compounds produce a variety of genotoxic effects. They are direct acting mutagens, increase DNA synthesis in rat hepatocytes, induce neoplastic transformation in mouse BALB/c3T3 cells and cause DNA single strand breaks, sister chromatid exchanges and mutations in human fibroblasts. The above findings suggest that a major factor in the causation of cancer of the large bowel in the human may have been found. However, thus far, a successful demonstration of fecapentaene-induced carcinogenesis in vivo has not been accomplished. Major problems that could account for these negative results have been defective handling of the fecapentaenes which are very labile compounds; inappropriate solvents; and inadequate animal models. The primary objective of the present proposal is to determine if fecapentaenes can produce a full or partial neoplastic response in the mucosa of the large bowel in experimental animals. Methodology for preventing decomposition of the fecapentaene will be employed. Short-term in vivo test systems will be used to determine the solvent, delivery conditions and dose schedule most likely to result in a carcinogenic response. These include assessment of expansion of the proliferative compartment of the crypts of the large bowel, determination of the presence of increased mitotic activity, studies of formation of nuclear aberrations, and studies of formation of aberrant crypts. Employing optimal conditions ascertained from the above, carcinogenesis studies will be undertaken to determine if fecapentaene: (1) is a full carcinogen, (2) is a tumor initiator, (3) is a tumor promoter, (4) can cause tumor progression, and/or (5) has syncarcinogenic properties in the mucosa of the large bowel. If positive results are obtained, they could form a basis evaluating the carcinogenic hazard from fecapentaenes and means of its prevention.