ASSESSMENT OF GENETIC DAMAGE INDUCED BY CHEMOTHERAPY

日益复杂和有效的化疗方式已经 导致正在被治愈的患者数量迅速增加 癌症。化疗的主要副作用之一是 性腺功能受损。在目前的研究中，几种不同的 将使用各种方法来研究MOPP引起的性腺毒性 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。这些药物包括氮气、芥末、 长春新碱、长春新碱、强的松(MOPP)和阿霉素、博莱霉素、 长春花碱和达卡巴津(ABVD)。这两种联合用药 治疗在产生完全缓解方面是有效的 80%的接受治疗的患者。然而，ABVD似乎引起了相当大的 比MOPP的生殖细胞毒性小。这些研究分为两个主要部分 部分：人体研究和实验动物研究。人文科学 将涉及精子数量、精子活力、精子形态的测定 以及精液样本中的染色体组成 用MOPP和ABVD治疗。前两个终结点将提供指示 而后两者将提供有关 诱发的遗传损伤。此外，患者的生育史， 在治疗期间和治疗后，将被记录下来，以便 两个治疗组的后代的出生缺陷可以进行比较。 对实验动物的研究将包括对每种药物的治疗 单次和多次注射，以及临床上的治疗 等价表使药物的协同或拮抗作用 在组合中使用可以确定。比较两种情况下的 人类和小鼠的生发损伤将是一个外推因素 将会被确定。对实验动物的研究也将允许 单药对干细胞产生影响的测定 杀戮、基因损伤和特定阶段的毒性。因此，上述 研究代表了对选定的 用于精子发生的化疗药物的数量。调查结果： 预计本研究将为以下方面提供有价值的信息 暴露在这些疗法中的抗受精和遗传风险。

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.