INDUCTION OF MICRONUCLEI AND GRANULAR CHROMATIN CONDENSATION IN HUMANSKIN FIBROBLASTS INFLUENCED BY CISPLATIN (CIS-DDP) IN-VITRO

Chromosomal damage was evaluated by quantification of micronuclei (MN) in two cell lines of human skin fibroblasts treated with different co ncentrations of cisplatin (ranging from 2 to 80 mu mol/l) over the fol lowing time intervals: 2, 24 and 48 h. The formation of micronuclei wa s dependent upon the concentration of cis-DDP as well as on the durati on of exposure. The dose-response curve for micronuclei in treated cel ls revealed a bell shape with the maximum at 12.5 mu mol/l cis-DDP. Th e results were compared with another toxicological phenomenon, granula r condensation of nuclear chromatin. This change, which was closely re lated to apoptosis in the cells exposed to cis-DDP, occurred at 5 mu m ol/l. The degree of condensation of nuclear chromatin depended on the concentration of cis-DDP. In contrast to the observations for micronuc lei, the dose-effect relationship was linear up to the highest tested concentration (80 mu mol/l). This change was primarily due to the dura tion of cis-DDP treatment. Our results showed the comparison between m icronucleus formation and granular condensation of nuclear chromatin, as two morphological manifestations of cisplatin-induced DNA damage.