6533b83afe1ef96bd12a78b3

RESEARCH PRODUCT

INFLUENCE OF α-6-DEOXY-5-OXYTETRACYCLINE ON SOME PHARMA-COLOGICAL CHARACTERISTICS OF DAUNOMYCIN

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(1) Treatment with doxycyline substantially reduces the acute toxicity of daunomycin to the mouse. Treatment with doxycycline alters the distribution of daunomycin amongst the body tissues of the mouse. The ability of the isolated kidney to bind the daunomycin is enhanced by pretreatment with doxycycline. This observation is in agreement with the phenomenon noted in vivo with the same organ. (2) The antineoplastic activity of daunomycin, tested in vivo in mice bearing Sarcoma 180 is not modified by treatment with doxycyctine, nor does doxycycline modify the inhibition of DNA synthesis in isolated Sarcoma 180 cells by daunomycin. (3) The experiments carried out on isolated cell, namely: (a) lack of interactions between daunomycin and doxycycline on the incorporation of thymidine into DNA, (b) no modifications in the uptake and retention of daunomycin by cells pretreated with doxycyline, suggest the hypothesis that the similar pharmacological behavior of the two molecules with regard to the tumor is due to 2 kinds of receptors that are affected differently by the two drugs. (4) The decrease in the acute toxicity of the antibiastic drug might be due to an interaction between doxycycline and those receptors of the toxic effect which are normally affected by daunomycin in the animals not treated with doxycycline.