Lerman M I, Abakumova O Iu, Kutsenko N G, Podobed O V
Biokhimiia. 1979 Apr;44(4):699-704.
Injection of 3,4-benz(a)pyrene, methyl nitrosourea and phenobarbital into healthy mice of the C3HA line results in a rapid, sharp increase of [14C]-thymidine incorporated into liver microsomal DNA, accompanied by a suppression of nuclear DNA synthesis. In the liver of neoplastic mice and in the ascite cells of hepatoma 22A the system of microsomal DNA synthesis was insensitive to the injection of methyl nitrosourea. Cycloheximide and puromycin, which strongly inhibited nuclear DNA synthesis, had no effect on the synthesis of microsomal DNA. Stimulation of [14C]-thymidine incorporation into microsomal DNA after injection of methyl nitrosourea and 3,4-benz(a)pyrene may be accounted for not only by an increase of the DNA reparation processes, since caffeine, the inhibitor of post-replicatory reparation of DNA, did not eliminate the induction of microsomal DNA synthesis in the liver. Hydroxyurea in combination with methyl nitrosourea and phenobarbital significantly suppressed the synthesis of nuclear DNA in the liver and did not affect the synthesis of mtDNA; the stimulating effects of these inducers on the synthesis of microsomal DNA was thereby removed. This is indicative of independence of synthesis of microsomal DNA on that of nuclear DNA and mtDNA. Different specific radioactivities of microsomal, nuclear and mtDNAs in the regenerating mouse liver on the 5th, 10th and 15th post-hepatectomy days may be due to different metabolic stability of these DNAs. A possible role of microsomal DNA as a xenobiotic system component is discussed.
向C3HA系健康小鼠注射3,4-苯并(a)芘、甲基亚硝基脲和苯巴比妥,会导致掺入肝微粒体DNA中的[14C]-胸腺嘧啶核苷迅速、急剧增加,同时核DNA合成受到抑制。在肿瘤小鼠的肝脏和肝癌22A的腹水细胞中,微粒体DNA合成系统对甲基亚硝基脲的注射不敏感。强烈抑制核DNA合成的环己酰亚胺和嘌呤霉素对微粒体DNA的合成没有影响。注射甲基亚硝基脲和3,4-苯并(a)芘后,[14C]-胸腺嘧啶核苷掺入微粒体DNA的刺激作用可能不仅是由于DNA修复过程的增加,因为DNA复制后修复的抑制剂咖啡因并没有消除肝脏中微粒体DNA合成的诱导。羟基脲与甲基亚硝基脲和苯巴比妥联合使用可显著抑制肝脏中核DNA的合成,且不影响线粒体DNA的合成;从而消除了这些诱导剂对微粒体DNA合成的刺激作用。这表明微粒体DNA的合成独立于核DNA和线粒体DNA的合成。肝切除术后第5、10和15天再生小鼠肝脏中微粒体、核和线粒体DNA的不同比放射性可能是由于这些DNA的代谢稳定性不同。本文讨论了微粒体DNA作为外源性物质系统成分的可能作用。