NEW ANTITUMOR DRUG CYCLOPLATAM INDUCES MICRONUCLEI IN THE BONE MARROW OF MICE

Abstract

Cycloplatam is a new antitumor drug of the group of platinum- containing preparations, which was originally synthesized in Russia [1]. Experiments on mice with inoculated model tumors showed a high antitumor activity of cycloplatam without nephrotoxicity [2]. The acute toxicity of cycloplatam was lower than that of cisplatin and carboplatin – the well-known platinum-containing drugs used in clinical oncology [3]. At the same time, the antitumor activity of cycloplatam under the experimental conditions studied exceeded that of carboplatin [3]. Now cycloplatam is in the second stage of clinical testing in Russia and Armenia. The drug already showed good clinical results in the treatment of lung, ovarian, and prostate cancers [2, 3]. It is commonly believed that the main mechanism of the antitumor action of platinum-containing drugs is related to the drug’s reaction with DNA. The interaction violates the secondary structure of DNA, which results in the formation of inter- and intrastrand crosslinks in the double-strand molecule [4] and leads eventually to a clastogenic (chromosome damage) effect [5]. The mutagen activity of platinum-containing drugs was confirmed by the Ames test on salmonellas, by tests on the bone marrow of rats and mice, and by in vitro experiments on human lymphocytes [6 – 8]. Similar to cisplatin, cycloplatam induces DNA crosslinking in cells of calf thymus and E. coli, which is evidence of the possible mutagenicity [9, 10]. However, this property was not verified by a micronuclear test on the bone marrow cells of mice – the main method for determining the mutagen properties of drugs [11]. The aim of this study was to fill the gap.