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.
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Authors | Armen Nersesyan, Emanuela Perrone, Paola Roggieri, Claudia Bolognesi |
Journal | Anti-cancer drugs
(Anticancer Drugs)
Vol. 17
Issue 3
Pg. 289-95
(Mar 2006)
ISSN: 0959-4973 [Print] England |
PMID | 16520657
(Publication Type: Journal Article)
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Chemical References |
- Organoplatinum Compounds
- cycloplatam
- Carboplatin
- Cisplatin
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Topics |
- Carboplatin
(pharmacology)
- Cisplatin
(pharmacology)
- Female
- Humans
- In Situ Hybridization, Fluorescence
- Lymphocytes
(drug effects)
- Male
- Micronuclei, Chromosome-Defective
(chemically induced)
- Micronucleus Tests
- Organoplatinum Compounds
(pharmacology)
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