DNA-蛋白交联物与药物相关性白血病的关系

Relationship between DNA-Protein Crosslinks and Drug Relative Leukemia

目的研究DNA-蛋白交联物与化学因素相关性白血病发生、发展之间的关系。方法由整体动物实验及体外实验两部分组成。整体动物实验包括:①乙双吗啉相关姓白血病动物模型的制备,参照山东大学齐鲁医院血液病室建立的方法进行。纯系615小鼠随机分为1、2及4 mg剂量染毒组及对照组,染毒组连续灌胃染毒2个月;对照组同时给予等量蒸馏水,观察染毒不同时间小鼠外周血象及骨髓象的变化;②外周血白细胞及骨髓细胞DNA的提取及定量参照有关生物化学方法进行;③DNA-蛋白交联物的测定采用酪氨酸125I后标记法进行。体外实验:①体外染毒体系的建立;②DNA-蛋白交联物的测定。结果乙双吗啉染毒小鼠白血病发病率明显增高,其发病率分别为:1 mg组15%,2 mg组25%,3 mg组25%,与对照组相比,差异有非常显著性(P<0.01)。整体动物实验和体外实验均表明,乙双吗啉染毒可使小鼠DNA-蛋白交联物明显增加,与对照组相比,差异有非常显著性(P<0.01)。结论在化学因素相关性白血病的发生、发展过程中,DNA-蛋白交联物可能起重要作用。

[Objective]To study the relationship between DNA- protein crosslinks and drug relative leukemia. [Methods]In vivo experiment and in vitro experiment were carried out. The in vivo experiment included four parts. ① Preparation for animal poisoning model; ② Extraction and quantitation of DNA from peripheral blood leucocyte of mice; ③Detennination of DNA - protein crosslinks. The in vitro experiment included three parts. ①Establishment of poisoning system in vitro; ① Determination of DNA - protein crosslinks. [Results]The leucemia morbidity highly increased after administration with bimolane （the morbidity of the lmg group was 15% and that of the 2mg group and 3rag group were 25 % and 25 % respectivel）. Both the two experiments indicated that administration with bimolane might increase the DNA- protein crosslinks of the mice, the difference was significant compared with the control group （ P 〈 0.01 ）. [ Conclusion] DNA - protein crosslinks might play a very important role in the process of the occurrence and development of chemical factors relative leukemia.