Cytogenetic toxicity of cycloplatam in human lymphocytes: Detection by the micronucleus test and fluorescence in situ hybridization

Armen Nersesyan, Emanuela Perrone, Paola Roggieri, Claudia Bolognesi

Research output: Contribution to journalArticle

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+ or C- MN was observed for cisplatin and carboplatin compared to the controls. A statistically significant (P- 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.

Original languageEnglish
Pages (from-to)289-295
Number of pages7
JournalAnti-Cancer Drugs
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 2006

Keywords

  • Aneugenic effects
  • Carboplatin
  • Cisplatin
  • Clastogenic damage
  • Cycloplatam
  • Cytogenetic effects
  • Fluorescence in situ hybridization
  • Genotoxicity
  • Micronucleus test
  • Platinum drugs

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

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