[Effects of daunorubicin and its nitroxyl analog on the synthesis of nucleic acids]

Abstract

The impact of daunorubicin, emoksil in sublethal doses and daunorubicin mixtures with a nitroxyl radical of 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (NR) on synthesis of DNA and RNA in some organs of rats was studied. Daunorubicin and emoksil induced marked (by 80 to 90%) inhibition of DNA synthesis in all the examined organs even within the first hours of administration. In the heart, DNA synthesis remained lower by the end of the experiment. In the spleen its partial recovery up to 40 to 60% of the control level was observed. In the liver the synthesis was stimulated in 24 hours. Its highest stimulation was recorded with the use of emoksil and daunorubicin in combination with NR. After administration of daunorubicin the maximum synthesis of DNA exceeded the control level 2.5 times. Addition of NR lowered 2-fold inhibition of DNA synthesis by daunorubicin within the first hours. It was of interest that the anthracyclines appeared to markedly stimulate RNA synthesis in the spleen, the fact not described in the literature. The stimulation of DNA synthesis in the liver was supposed to be one of the components of the compensatory mechanisms engaged by the cell in response to the drug's damaging effect.