[Cytogenetic analysis of the effects of selected 2d generation cytostatics (iproplatin and oxoplatin) on human peripheral lymphocytes in vitro].

Abstract

Cytostatic effect of Iproplatinum (CHIP, cis-dichlorotrans-dihydroxy-bis-isopropylaminoplatinic complex) and Oxoplatinum (oxo-Pt, cis-diamin-dichloro-trans-dihydroxyplatinic complex) is studied as influencing genetic structures of in vitro human peripheral lymphocytes. Both mentioned substances are classed as prospective cytostatics with satisfactory effect on various tumors, and both undergo now preclinical tests in our country. They are supposed to cause less undesired side effects in comparison with previous preparation of this range--cisplatinum (cis-DDP; Platidiam). The genotoxicity of both substances is examined using the short-term test (72 hrs.), which means a cultivation of raw human peripheral blood modified according to Macek (1965). To set the testing scheme, five concentrations of substances (0, 5, 12, 60 and 120 mumol.l-1) were selected as well as three time intervals of action of a substance (3, 6 and 24 hrs.) prior the expiration of cultivation time, i.e. before the mitotic cycle stop in c-metaphase. Concentrations were determined estimating cisplatinum's dosage to patients. The concentration value 120 mumol.l-1 responds in theory to a single therapeutic dose administration of Platidiam. However, in praxis this concentration is never achieved in organism (resp. protein-binding effect). In accordance with mice LD50 values, both the Iproplatinum and Oxoplatinum showed experimentally 10 times less toxicity than cis-DDP. Cytogenetic changes were evaluated by microscopy in peripheral lymphocytes (predominantly the occurrence of chromosome abnormalities in metaphase), and mitotic activity was as well identified.

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