PMID- 16520657 OWN - NLM STAT- MEDLINE DCOM- 20061204 LR - 20190917 IS - 0959-4973 (Print) IS - 0959-4973 (Linking) VI - 17 IP - 3 DP - 2006 Mar TI - Cytogenetic toxicity of cycloplatam in human lymphocytes: detection by the micronucleus test and fluorescence in situ hybridization. PG - 289-95 AB - 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. FAU - Nersesyan, Armen AU - Nersesyan A AD - Cancer Research Center, Yerevan, Armenia. FAU - Perrone, Emanuela AU - Perrone E FAU - Roggieri, Paola AU - Roggieri P FAU - Bolognesi, Claudia AU - Bolognesi C LA - eng PT - Journal Article PL - England TA - Anticancer Drugs JT - Anti-cancer drugs JID - 9100823 RN - 0 (Organoplatinum Compounds) RN - 109837-67-4 (cycloplatam) RN - BG3F62OND5 (Carboplatin) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Carboplatin/pharmacology MH - Cisplatin/pharmacology MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lymphocytes/*drug effects MH - Male MH - Micronuclei, Chromosome-Defective/*chemically induced MH - Micronucleus Tests MH - Organoplatinum Compounds/*pharmacology EDAT- 2006/03/08 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/03/08 09:00 PHST- 2006/03/08 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/03/08 09:00 [entrez] AID - 00001813-200603000-00007 [pii] AID - 10.1097/00001813-200603000-00007 [doi] PST - ppublish SO - Anticancer Drugs. 2006 Mar;17(3):289-95. doi: 10.1097/00001813-200603000-00007.