Human Germ Line Effects From Zidovudine And Other Dideox

齐多夫定和其他 Dideox 对人类生殖系的影响

• 批准号: 6837363
• 负责人: JACK B BISHOP
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6837363
• 关键词: 2'3' dideoxynucleoside; AIDS therapy; DNA damage; HIV infections; antiAIDS agent; blood chemistry; chemoprevention; chromosome aberrations; clinical research; cytogenetics; drug adverse effect; drug screening /evaluation; fertility; fluorescent in situ hybridization; human subject; male; mutagen testing; mutagens; reproductive system pharmacology; sperm; sperm analysis; zidovudine

Antiretroviral therapies with dideoxynucleosides, such as ZDV, have not been adequately examined for potential reproductive or long term mutagenic effects in humans. Such investigations are warranted given that genetic damage in humans and genetic plus reproductive effects in animals have been reported following ZDV exposure. The data obtained from such investigations help individuals and their physicians make more informed risk/benefit decisions about the use of these therapies. A total of 26 HIV positive males who were preparing to start nucleoside-containing antiretroviral therapy were enrolled in a study designed to measure cytogenetic damage in blood lymphocytes, and fertility and cytogenetic parameters in sperm. Blood and semen samples were obtained prior to the start of therapy and one to three times during treatment. Blood lymphocytes were processed for chromosome analysis and conventional analyses were performed on semen samples. Sperm smears were evaluated for abnormal morphology, and for aneuploidy using a novel fluorescence in situ hybridization (FISH) procedure. Sperm cells were also evaluated for chromosome breakage using another novel sperm-FISH assay. Analysis of the data revealed no significant treatment-related effects of antiretroviral therapy on lymphocyte or sperm cytogenetic parameters, or on semen volume or sperm concentration. However, sperm motility, viability, and morphology improved significantly with treatment. These findings suggest that nucleoside reverse transcriptase inhibitors, over a three-month period at currently recommended doses, do not adversely affect lymphocyte or sperm chromosomes, and may actually lead to improvements in semen quality. A manuscript by Robbins et al (2001) describing the results of this study was published in the Journal of Infectious Diseases volume 184:127-135. Studies have been conducted in collaboration with Dr. Miriam Poirier at NCI to look at a subset of our sperm samples for incorporation of AZT into sperm DNA. Results to date have been equivocal.

二乙氧基核苷（例如ZDV）的抗逆转录病毒疗法尚未对人类的潜在生殖或长期诱变作用进行充分检查。鉴于在ZDV暴露后，已经报道了人类的遗传损害和遗传加生殖作用，因此有必要进行此类研究。从此类调查中获得的数据可帮助个人及其医生对使用这些疗法做出更明智的风险/利益决定。一项研究旨在测量血液淋巴细胞中的细胞遗传学损伤，精子中的生育能力和细胞遗传学参数的研究，共有26名艾滋病毒阳性男性准备开始接受含核苷的抗逆转录病毒疗法。在开始治疗之前获得了血液和精液样本，在治疗期间获得了一到三次。处理血液淋巴细胞进行染色体分析，并对精液样品进行常规分析。评估了精子涂片的异常形态，并使用新型的荧光原位杂交（FISH）程序来评估非整倍性。还使用另一种新型的精子法测定法对精子细胞进行了染色体破裂的评估。对数据的分析表明，抗逆转录病毒治疗对淋巴细胞或精子细胞遗传学参数或精液量或精子浓度没有显着的治疗相关作用。但是，精子运动，生存力和形态随着治疗而显着改善。这些发现表明，核苷逆转录酶抑制剂在当前建议的三个月内，不会对淋巴细胞或精子染色体产生不利影响，实际上可能会改善精液质量。 Robbins等人（2001）的手稿描述了这项研究的结果，发表在《传染病杂志》第184：127-135卷中。已经与NCI的Miriam Poirier博士合作进行了研究，以研究我们的精子样本的一部分，以将AZT掺入精子DNA中。迄今为止的结果是模棱两可的。

项目成果

Evaluation of inter-scorer and inter-laboratory reliability of the mouse epididymal sperm aneuploidy (m-ESA) assay.

小鼠附睾精子非整倍性 (m-ESA) 测定的评分者间和实验室间可靠性评估。

• DOI: 10.1093/mutage/16.3.189
• 发表时间: 2001
• 期刊: Mutagenesis
• 影响因子: 2.7
• 作者: Schmid,TE;Lowe,X;Marchetti,F;Bishop,J;Haseman,J;Wyrobek,AJ
• 通讯作者: Wyrobek,AJ