CELLULAR GENETIC ASPECTS OF OPIATE USE

作为评估阿片类药物滥用的长期遗传影响计划的一部分， 研究替代物或拮抗剂的改善，一系列的压力， 已经开发了一种系统来测试电池处理电势的能力 突变危机 海洛因成瘾者的染色体频率增加 在未应激的白细胞培养物中的损伤和应激系统， 表明它们修复远紫外线损伤的能力也有缺陷， 通过程序外DNA合成和姐妹染色单体的改变来测量 交换反应。 紫外线的变化 经长期处理后，诱导的DNA修复和染色体畸变得到纠正 美沙酮维持治疗 为了进一步理解这些发现的含义， 计划进行研究，以评估修复紫外线损伤的第二个分析系统 并且还使用化学应激剂代替UV。 的速率 美沙酮逆转生化和细胞遗传学效应， 将确定化学和紫外线应力，并与所发现的速率进行比较 和纳洛酮 这些研究应该有助于确定 这些治疗方式在基因水平上的相对有效性。 在 结合体内实验，还将启动研究， 尝试在体外用成纤维细胞培养物重现这些发现， 探讨产生这些效应的机制。

As part of a program to evaluate long term genetic effects of opiate abuse and investigate amelioration with replacements or antagonists, a series of stress systems has been developed to test the capacity of the cell to handle potential mutagenic crises. Heroin addicts have an increased frequency of chromosome damage in unstressed leukocyte cultures and with the stress systems it can be shown that there is also a defect in their ability to repair far UV damage as measured by unscheduled DNA synthesis and an alteration in sister chromatid exchange response when stressed by UV and mitomycin C. The changes in UV induced DNA repair and chromosome aberrations were corrected after long term methadone maintenance. To further understand the implication of these findings studies are planned to evaluate repair of UV damage with a second assay system and also to use a chemical stress agent in place of UV. The rate at which methadone reverses both the biochemical and cytogenetic effects as measured with chemical and UV stresses will be determined and compared with the rates found for LAAM and naltrexone. These studies should be useful in determining the relative effectiveness of these treatment modalities at the genetic level. In conjunction with the in vivo experiments studies will also be initiated to attempt to reproduce these findings in vitro with fibroblast cultures to investigate the mechanism which produce these effects.