ABSTRACT
The treatment of exponentially-growing B16 melanoma cells with teniposide causes a dose- and time-dependent decrease of cell survival. By means of the nucleoid technique, the formation of double strand breaks was demonstrated in the nuclei of the treated cells, indicating a possible involvement of topoisomerase II. DNA double strand breaks were rapidly but ineffectively repaired. Morphometric and densitometric analyses showed that teniposide treatment causes a considerable increase of nuclear area, nuclear DNA and cell size, associated with a lowering of the mitotic index to less than one hundredth of that of the controls. The cytocidal effect of VM-26 can be potentiated by the addition of a non-lethal dose of lonidamine, whose synergism is particularly evident at low teniposide concentrations.
Subject(s)
Antineoplastic Agents/pharmacology , Indazoles/pharmacology , Podophyllotoxin/analogs & derivatives , Pyrazoles/pharmacology , Teniposide/pharmacology , Tumor Cells, Cultured/drug effects , Animals , Cell Division/drug effects , Cell Line , Cell Nucleus/drug effects , Cell Nucleus/ultrastructure , Cell Survival/drug effects , Clone Cells , Drug Interactions , Drug Screening Assays, Antitumor , Melanoma, Experimental , Mice , Mitotic Index/drug effects , Tumor Cells, Cultured/cytologyABSTRACT
A doxorubicin-lecithin preparation was tested in vitro on B16 melanoma and Lewis lung carcinoma cells, and in vivo on C57BL/6 mice inoculated with 3LL cells. Results obtained demonstrated that the preparation possesses the same antitumor activity as doxorubicin. The cardiotoxicity of doxorubicin and of the doxorubicin-lecithin association were studied for 120 days after the end of the treatments in Wistar rats inoculated once a week for 5 weeks with equivalent doses of the drugs. Myocardial lesions were observed in both the groups of animals, but their severity and extent were reduced in rats treated with the doxorubicin-lecithin association, and their onset was also delayed.