Induction of micronuclei and granular chromatin condensation in human skin 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 concentrations of cisplatin (ranging from 2 to 80 mumol/l) over the following time intervals: 2, 24 and 48 h. The formation of micronuclei was dependent upon the concentration of cis-DDP as well as on the duration of exposure. The dose-response curve for micronuclei in treated cells revealed a bell shape with the maximum at 12.5 mumol/l cis-DDP. The results were compared with another toxicological phenomenon, granular condensation of nuclear chromatin. This change, which was closely related to apoptosis in the cells exposed to cis-DDP, occurred at 5 mumol/l. The degree of condensation of nuclear chromatin depended on the concentration of cis-DDP. In contrast to the observations for micronuclei, the dose-effect relationship was linear up to the highest tested concentration (80 mumol/l). This change was primarily due to the duration of cis-DDP treatment. Our results showed the comparison between micronucleus formation and granular condensation of nuclear chromatin, as two morphological manifestations of cisplatin-induced DNA damage.
Jirsová
K
K
Laboratory of Cell Pathology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague.
Mandys
V
V
D002460:Cell Line; D002843:Chromatin / Q000187:drug effects*; D002945:Cisplatin / Q000633:toxicity*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048629:Micronuclei, Chromosome-Defective; D009153:Mutagens / Q000633:toxicity*; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D002843:Chromatin; D009153:Mutagens; D004247:DNA; D002945:Cisplatin