CANCER MODELS FOR DNA-INTERACTING DRUGS

该项目旨在提高慢性阻塞性肺疾病的治疗效果。 蒽环类药物(阿霉素、柔红霉素等)、AZQ及相关 通过改变它们在动物体内的新陈代谢变化。在……里面 荷瘤小鼠，将给予蒽环类药物 与抑制黄嘌呤氧化酶的别嘌醇联合使用 将蒽环类药物转化为苷元的酶。相同 该系统也代谢AZQ，将进行联合测试 与别嘌醇对荷瘤小鼠(L1210、P388等)的作用。AZQ 专门为脑瘤的化疗而设计的，将是 在动物身上进行了带有使药物灭活的救援剂的测试 系统性地(降低寄主毒性)，但影响很小或没有 关于脑肿瘤中的AZQ。与这些研究相关的是， 救助剂在骨髓细胞中的作用 脾细胞集落分析。阿司匹林的药代动力学和代谢研究 将描述AZQ在动物中的作用。不稳定因素的相互作用 蒽环类药物生物转化的中间产物， AZQ和类似的带有DNA的药物将进行研究 考虑到交叉链接和链间损伤。这些影响对 DNA将用DNA聚合酶α进行评估。

This project is intended to improve therapeutic efficacy of anthracyclines (Adriamycin, daunorubicin, etc.), AZQ, and related agents by altering their metabolic transformations in animals. In tumor bearing mice, anthracycline drugs will be given in combination with allopurinol which inhibits xanthine oxidase, an enzyme that converts the anthracyclines to aglycones. The same system also metabolizes AZQ and it will be tested in combination with allopurinol in mice with tumors (L1210, P388, etc.). AZQ specifically designed for chemotherapy of brain tumors, will be tested in animals with rescue agents that inactivate the drug systemically (to reduce host toxicity) but have little or no effect on AZQ in brain tumors. Associated with these studies, the effects of rescue agents in bone marrow cells with be tested by spleen colony assays. The pharmacokinetics and metabolism of AZQ in animals will be described. The interactions of labile intermediary products of biotransformation of anthracyclines, AZQ, and similar agents with DNA will be investigated with respect to cross-links and interstrand damage. These effects on DNA will be evaluated with DNA polymerase alpha.