title: Cytogenetic toxicity of cycloplatam in human lymphocytes: detection by the micronucleus test and fluorescence in situ hybridization.
abstract: Cycloplatam has been shown to be effective in the treatment of pleural mesothelioma, myeloma and ovarian carcinoma. Cycloplatam is not nephrotoxic with respect to the platinum-based anti-tumor agents. We have investigated the mechanism underlying the induction of micronuclei (MN) in human lymphocytes by cycloplatam compared to that by its parent drugs cisplatin and carboplatin. The cytokinesis-block micronucleus assay in human lymphocytes was applied in combination with fluorescence in situ hybridization (FISH) with an all-chromosome centromeric probe allowing discrimination between MN due to chromosomal fragments (centromere negative, C) and those containing whole chromosomes (centromere positive, C). A statistically significant increase of MN frequency (P<0.001) was detected for cisplatin, carboplatin and cycloplatam. However, cycloplatam was active at a much lower dose (0.1 micromol/l) than cisplatin or carboplatin (1 micromol/l). No significant increase in the frequency of C or C MN was observed for cisplatin and carboplatin compared to the controls. A statistically significant (P<0.001) increase in the percentage of C MN was observed in cycloplatam-treated cells. The results obtained suggest different mechanisms for cytogenetic damage induced by platinum drugs. Cycloplatam induces one type of MN and it could be considered a clastogenic agent, whereas cisplatin and carboplatin appear to induce both chromosome breakage and numerical chromosomal abnormalities.
authors.affiliation: Cancer Research Center, Yerevan, Armenia.
authors.forename: Armen
authors.initials: A
authors.lastname: Nersesyan
authors.forename: Emanuela
authors.initials: E
authors.lastname: Perrone
authors.forename: Paola
authors.initials: P
authors.lastname: Roggieri
authors.forename: Claudia
authors.initials: C
authors.lastname: Bolognesi
mesh_terms: D016190:Carboplatin / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009944:Organoplatinum Compounds / Q000494:pharmacology*
chemical_list: D009944:Organoplatinum Compounds; C055928:cycloplatam; D016190:Carboplatin; D002945:Cisplatin