Abstract
The ability of the antineoplastic agent epirubicin to induce aneuploidy and meiotic delay in the somatic and germinal cells of male mice was investigated by fluorescence in situ hybridization assay using labeled DNA probes and BrdU-incorporation assay. Mitomycin C and colchicine were used as positive controls for clastogen and aneugen, respectively, and these compounds produced the expected responses. The fluorescence in situ hybridization assay with a centromeric DNA probe for erythrocyte micronuclei showed that epirubicin is not only clastogenic but also aneugenic in somatic cells in vivo. By using the BrdU-incorporation assay, it could be shown that the meiotic delay caused by epirubicin in germ cells was approximately 48 h. Disomic and diploid sperm were shown in epididymal sperm hybridized with DNA probes specific for chromosomes 8, X and Y after epirubicin treatment. The observation that XX- and YY-sperm significantly prevailed over XY-sperm indicates missegregation during the second meiotic division. The results also suggest that earlier prophase stages contribute less to epirubicin-induced aneuploidy. Both the clastogenic and aneugenic potential of epirubicin can give rise to the development of secondary tumors and abnormal reproductive outcomes in cured cancer patients and medical personnel exposed to epirubicin.
Highlights
In cancer therapy, surgery, radiotherapy, and chemotherapy are used frequently
Epirubicin treatment at a dose of 3 mg/kg did not exhibit any significant differences in the frequency of MNPCE and polychromatic erythrocytes (PCE) frequencies compared to the solvent control (P.0.05)
No discrimination between MN induced in PCE and normochromatic erythrocytes (NCE) was required for fluorescent analysis of MN with fluorescence in situ hybridization (FISH) because the NCE only minimally contributed to the total MN number
Summary
Of the chemotherapeutics in clinical use, anthracyclines have a wide spectrum of antitumor activity and are clearly the most useful cancer drugs that are natural products [1]. Members of this drug group are highly active against epithelial tumors, such as carcinomas of the breast, lung, thyroid, and stomach, and against mesenchymal malignancies such as Hodgkin’s and non-Hodgkin’s lymphoma, multiple myeloma, acute lymphocytic and myelogenous leukemia, and sarcomas. Epirubicin (49-epi-doxorubicin) differs from doxorubicin in the steric position of the 49-OH group This drug is commonly used because it has an equivalent spectrum of antitumor action to that of doxorubicin but exhibits less systemic and cardiac toxicity [2]
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