Margeli A, Theocharis S, Skaltsas S, Skopelitou A, Kittas C, Mykoniatis M, Varonos D
Department of Experimental Pharmacology, Medical School, University of Athens, Greece.
Arch Toxicol. 1994;68(2):85-90. doi: 10.1007/s002040050039.
Cadmium is a rare element that is nevertheless widely distributed throughout the biosphere and its toxic effects are becoming potentially more serious due to industrialization. Liver regeneration can be considered as a spectacular example of controlled tissue increase. In this study we examined the effect of cadmium pretreatment, administered 24 h before partial hepatectomy, on the liver regenerative process in rats, at different time intervals. The rate of 3H thymidine incorporation into hepatic DNA and the activity of the enzyme thymidine kinase were used as indices of liver proliferative capacity. Thymidine kinase, the rate-determining enzyme of DNA biosynthesis, was suppressed during the first hours following partial hepatectomy in the liver of cadmium pretreated animals. DNA biosynthesis was also strongly decreased in cadmium pretreated animals, by delaying the first peak of liver regeneration, compared with the partially hepatectomized ones. Biochemical parameters, mitotic index and proliferating cell nuclear antigen staining were also coestimated. The above data suggest that cadmium pretreatment suppressed the hepatic regenerative process, probably due to the inhibition of thymidine kinase.
镉是一种稀有元素,但在整个生物圈中广泛分布,并且由于工业化,其毒性作用可能变得更加严重。肝脏再生可被视为受控组织增加的一个显著例子。在本研究中,我们在大鼠部分肝切除术前24小时给予镉预处理,并在不同时间间隔观察其对肝脏再生过程的影响。将3H胸苷掺入肝DNA的速率和胸苷激酶的活性用作肝脏增殖能力的指标。胸苷激酶是DNA生物合成的限速酶,在镉预处理动物肝脏部分肝切除后的最初几个小时内受到抑制。与部分肝切除的动物相比,镉预处理动物的DNA生物合成也因延迟肝脏再生的第一个峰值而显著降低。还共同评估了生化参数、有丝分裂指数和增殖细胞核抗原染色。上述数据表明,镉预处理抑制了肝脏再生过程,可能是由于胸苷激酶受到抑制。