Sazuka Y, Tanizawa H, Takino Y
School of Pharmaceutical Sciences, University of Shizuoka.
Jpn J Cancer Res. 1989 Oct;80(10):1000-5. doi: 10.1111/j.1349-7006.1989.tb01640.x.
We examined whether the cause of the remarkable decreases in the activities of lipid peroxidation-preventive enzymes in the heart of adriamycin (ADR)-treated mice might be related to inhibition of DNA, RNA or protein biosynthesis. It was found that biosyntheses of DNA, RNA and protein in the heart, liver and kidney of mice were markedly inhibited by ADR (15 mg/kg, ip). The inhibitory effects of ADR on each type of biosynthesis were particularly marked in the heart among the tissues examined. Strong correlations between the percentage inhibition of DNA and protein biosynthesis by ADR, and the percentage decrease in the activities of lipid peroxidation-preventive enzymes were observed in the heart, liver, kidney and lung, especially for the decrease of glutathione peroxidase activity and the inhibition of DNA and protein biosyntheses. We also found that marked decreases of DNA, RNA and protein biosynthesis in ADR-treated mice occurred not only in the heart but also in tumor tissues. From these results, we conclude that the increment of cardiac lipid peroxide in ADR-treated mice, which is closely related to the cardiotoxicity of ADR, results from inhibition of DNA, RNA and protein biosyntheses after the distribution of ADR.
我们研究了阿霉素（ADR）处理的小鼠心脏中脂质过氧化预防酶活性显著降低的原因是否与DNA、RNA或蛋白质生物合成的抑制有关。结果发现，ADR（15mg/kg，腹腔注射）可显著抑制小鼠心脏、肝脏和肾脏中的DNA、RNA和蛋白质生物合成。在所检查的组织中，ADR对每种生物合成类型的抑制作用在心脏中尤为明显。在心脏、肝脏、肾脏和肺中，观察到ADR对DNA和蛋白质生物合成的抑制百分比与脂质过氧化预防酶活性的降低百分比之间存在很强的相关性，尤其是谷胱甘肽过氧化物酶活性的降低以及DNA和蛋白质生物合成的抑制。我们还发现，ADR处理的小鼠中DNA、RNA和蛋白质生物合成的显著降低不仅发生在心脏，也发生在肿瘤组织中。从这些结果中，我们得出结论，ADR处理的小鼠心脏中脂质过氧化物的增加与ADR的心脏毒性密切相关，这是ADR分布后DNA、RNA和蛋白质生物合成受到抑制的结果。
