Carboplatin-induced micronuclei formation in non-neuronal cells of rat foetal dorsal root ganglia cultured in vitro and comparison with another anticancer drug--cisplatin.
Carboplatin-induced chromosomal damage was evaluated in two types of non-neuronal cells, fibroblasts and Schwann cells, migrating from rat foetal dorsal root ganglia (DRG) in explant cultures by quantification of micronuclei (MN). Evaluation of granular condensation of nuclear chromatin, another toxicological phenomenon, closely related to activation of apoptosis, was performed to compare genotoxic and cytotoxic action of the drug. Both changes were dependent upon the concentration of the drug as well as on the exposure time. Dose-response curves for micronuclei in fibroblasts revealed normal distribution with the maximum at 100, 25 and 5 mumol/l after 24, 48 and 72 hours treatment of carboplatin, respectively. The maximum number of micronuclei in Schwann cells was obtained at 25, 25 and 12.5 mumol/l at the same exposure time. Micronucleation of fibroblasts represented 293, 382 and 376% of control values and in Schwann cells 366, 819 and 1667%, respectively. These results were compared with the data obtained in our previous experiments where identical cell types were influenced by cisplatin. The maximal micronucleation in fibroblasts treated with cisplatin reached 208-385% of control values at the same intervals. The maximal number of micronuclei in Schwann cells was induced by cisplatin at the dosis about 20 times lower compared to carboplatin (ranged from 2 to 0.75 mumol/l) and represented 914, 1032, 1693% of control values. Our results suggest that Schwann cells are more sensitive to platinum drugs than fibroblasts, especially to cis-DDP. Moreover, carboplatin revealed delayed toxic effect in comparison with cisplatin. This finding could contribute to the explanation of different neurotoxic potential of both cytostatics.
Jirsová
K
K
Laboratory of Cell Pathology, Academy of Sciences of Czech Republic, Prague.
Mandys
V
V
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D016190:Carboplatin / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D046508:Culture Techniques; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D015162:Micronucleus Tests; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000187:drug effects
D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin