Kutsenko N G, Abkumova O Iu, Lerman M I, Sokolova I S, Serebrianyi A M
Biokhimiia. 1976 Nov;41(11):1987-2000.
Alkylation DNA reparation kinetics and the disintegration of alkylated RNA, proteins and lipids in liver, spleen and brain of intact and 22A hepatomic mice after a injection of 1-14C-nitrosomethylurea at a therapeutic dose are studied. The tissue studied are different in their macromolecules and lipids alkylation, in DNA reparation and RNA, protein and lipid degradation rates. Possible correlation between the time of the occurrence of DNA damages and the frequency of tumour emergence in different tissues is discussed. It is found that normal cells eliminate more rapidly degraded RNA, protein and lipid molecules and more rapidly repair DNA damages as compared with 22A hepatoma cells. It is suggested to be due to more rapid macromolecule metabolism in normal cells which specifies a selective sensitivity of tumour cells to alkylating agents and nitrosoalkylureas. The time of the occurrence of damages induced with alkylating agents and nitrosomethylureas is supposed to be a critical parameter in processes resulting in the selective sensitivity of normal and tumour cells.
研究了完整小鼠和22A肝癌小鼠在注射治疗剂量的1-¹⁴C-亚硝基甲基脲后,肝脏、脾脏和大脑中DNA烷基化修复动力学以及烷基化RNA、蛋白质和脂质的分解情况。所研究的组织在其大分子和脂质烷基化、DNA修复以及RNA、蛋白质和脂质降解速率方面存在差异。讨论了不同组织中DNA损伤发生时间与肿瘤出现频率之间可能的相关性。发现与22A肝癌细胞相比,正常细胞能更快速地清除降解的RNA、蛋白质和脂质分子,并且能更快速地修复DNA损伤。这被认为是由于正常细胞中大分子代谢更快,这决定了肿瘤细胞对烷化剂和亚硝基烷基脲的选择性敏感性。烷基化剂和亚硝基甲基脲诱导损伤的发生时间被认为是导致正常细胞和肿瘤细胞选择性敏感性的过程中的一个关键参数。