K. Jirsova et V. Mandys, INDUCTION OF MICRONUCLEI AND GRANULAR CHROMATIN CONDENSATION IN HUMANSKIN FIBROBLASTS INFLUENCED BY CISPLATIN (CIS-DDP) IN-VITRO, Mutation research, 310(1), 1994, pp. 37-44
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.