Effect of adriamycin on DNA, RNA and protein biosyntheses in mouse tissues, in connection with its cardiotoxicity.
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.
Sazuka
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka.
Tanizawa
H
H
Takino
Y
Y
D015250:Aclarubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis*
C011157:aclacinomycins; D012313:RNA; D015250:Aclarubicin; D004317:Doxorubicin; D004247:DNA; D005979:Glutathione Peroxidase; D003630:Daunorubicin