Cytoprotective activity of amifostine on cultured human lymphocytes exposed to irinotecan.
Irinotecan (camptothecin, CAM) is a topoisomerase-I inhibitor with a well established action in the chemotherapy of colorectal and ovarian cancer. Hematological and intestinal toxicity are commonly noted in patients treated with CAM. In this study, we examined the cytoprotective efficacy of amifostine (ethyol, ETH) against chromosomal damage induced by this drug on cultured peripheral human lymphocytes. Cultured lymphocytes were exposed to CAM (50 and 100 ng/ml of final concentrations) without or with ETH (in concentrations varying between 40 and 800 microg/ml of final culture volume). CAM's genotoxicity was quantified by counting the Sister Chromatid Exchange (SCEs) rate. The mitotic index (MI) and proliferation rate index (PRI) were also assessed. The SCE rate was increased following incubation with CAM, but the combined treatment of CAM with ETH significantly reduced the SCE formation, especially when ETH added at high concentrations. The MIs and PRIs remained also unaltered in cultures with CAM, but MIs were reduced with the combined treatment at high ETH concentrations. Clinical studies are required to assess the predicted benefits from ETH in patients receiving CAM.
Lialiaris
Th S
TS
Department of Genetics, Faculty of Medicine, Demokrition University of Thrace, Alexandroupolis 68100, Greece. lialiari@med.duth.gr
Kotsiou
E
E
Pouliliou
S
S
Kareli
D
D
Makrinou
H
H
Kouskoukis
A
A
Papachristou
F
F
Koukourakis
M
M
D000293:Adolescent; D000328:Adult; D004999:Amifostine / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D000077146:Irinotecan; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D055815:Young Adult
D016587:Antimutagenic Agents; D004791:Enzyme Inhibitors; D011837:Radiation-Protective Agents; D000077146:Irinotecan; D004999:Amifostine; D002166:Camptothecin