ASSESSMENT OF GENETIC DAMAGE INDUCED BY CHEMOTHERAPY

日益复杂和有效的化疗方式， 导致越来越多的病人被治愈， 癌化疗的主要副作用之一是 性腺功能受损。在本研究中，几个不同的 方法将用于研究MOPP诱导的性腺毒性 和ABVD疗法。这是两种最有效和最常用的药物 霍奇金淋巴瘤的治疗方法这些药物包括氮，芥子气， 长春新碱，甲基苄肼和泼尼松（MOPP）和阿霉素，博莱霉素， 长春碱和达卡巴嗪（ABVD）。这两种联合用药 治疗有效地产生完全缓解， 80%的患者接受治疗。然而，ABVD似乎引起了相当大的 生殖细胞毒性低于MOPP。研究分为两大部分 部分：人体研究和实验动物研究。 人类研究 将包括精子计数、精子活力、精子形态的测定 和染色体组成的患者精液样本中， 用MOPP和ABVD治疗。前两个终点将指示 而后两者将产生有关生育能力的信息， 导致遗传损伤。此外，患者的生殖史， 在治疗期间和治疗后，将被记录， 可以比较两个处理组的后代的出生缺陷。 对实验动物的研究将包括用每种药剂进行的治疗， 单次和多次注射，以及临床治疗 等效时间表，以便药物的协同或拮抗作用 可以组合使用。 比较的程度 将在人类和小鼠中产生生殖损伤， 将被确定。对实验动物的研究也将允许 确定单个药物对产生干细胞的影响 杀死，遗传损伤;和阶段特异性毒性。因此上述 这些研究是对选定的一种 化疗药物对精子发生的影响。结果 预计本研究将提供有关以下方面的宝贵信息： 暴露于这些疗法的抗肿瘤和遗传风险。

The increasingly complex and effective modalities of chemotherapy has resulted in a rapidly increasing number of patients that are being cured of cancer. One of the major side effects of chemotherapy has been the impairment of gonadal functions. In the present study, several different approaches will be used to investigate gonadal toxicity induced by MOPP and ABVD therapies. These are the two most effective and commonly used drugs treatments for Hodgkin's lymphoma. These drugs include nitrogen, mustard, vincristine, procarbazine and prednisone (MOPP) and adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Both of these combination drug treatments are effective in producing complete remission in approximately 80% of the treated patients. However, ABVD appears to cause considerable less germ-cell toxicity than MOPP. The studies are divided into two major parts: human studies and studies with experimental animals. Human studies will involve determinations of sperm count, sperm motility, sperm morphology and chromosomal constitutions in semen samples of patients that have been treated with MOPP and ABVD. The former two endpoints will give indications of fertility whereas the latter two will yield information about the induced genetic damage. In addition, reproductive histories of patients, during and after the therapies, will be recorded so that the incidence of birth defects in the offspring of the two treatment groups can be compared. Studies on experimental animals will include treatments with each agent in single and multiple injections, as well as treatments with clinically equivalent schedules so that synergistic or antagonistic effects of drugs used in combination can be determined. Comparisons between the extent of germinal damage in human and mice will be made and an extrapolation factor will be determined. Studies with experimental animals will also allow determination of the effects of individual drugs on producing stem cell killing, genetic damage; and stage-specific toxicity. Therefore, the above studies represent a comprehensive assessment of the effects of a selected number of chemotherapeutic drugs on spermatogenesis. Results from the present study are expected to provide valuable information with regard to the antifertilizing and genetic risks from exposure to these therapies.