Attenuation of cytogenetic effects by erythropoietin in human lymphocytes in vitro and P388 ascites tumor cells in vivo treated with irinotecan (CPT-11).
Erythropoietin (EPO) is a protein widely used against drug induced anemia at cancer patients. Irinotecan (CPT-11) is a genotoxic topoisomerase I inhibitor. We investigated the genotoxic, cytostatic and cytotoxic effects of EPO in the presence and in the absence of CPT-11 in human lymphocytes in vitro and in ascites cells of P388 leukemia in vivo. The levels of genotoxicity, cytostaticity and cytotoxicity were evaluated in human lymphocytes in vitro, and in P388 ascites tumor cells in vivo. The results show that EPO is not genotoxic. Unlikely to EPO, CPT-11 caused severe genotoxic, cytostatic and cytotoxic effects by significantly increasing SCE levels and decreasing PRI and MI values in peripheral lymphocytes in vitro and in P388 ascites tumor cells in vivo. Adding EPO in human lymphocyte cultures in vitro and in P388 leukemia bearing mice in vivo in the presence of CPT-11 decreased SCEs levels and increased PRIs and MIs were observed compared with cells treated either in vitro or in vivo with CPT-11 alone, which shows that EPO protected cells from the toxic action of CPT-11. EPO's protective action on human peripheral lymphocytes in vitro and P388 cells in vivo from the topoisomerase I inhibitor CPT-11, lead us to propose it as a geno- and cytoprotective agent.
Digkas
E
E
Dept. of Genetics, School of Medicine, Demokrition University of Thrace, GR 68100 Alexandroupolis, Greece.
Kareli
D
D
Chrisafi
S
S
Passadaki
T
T
Mantadakis
E
E
Hatzimichail
A
A
Vargemezis
V
V
Lialiaris
Th
T
D000293:Adolescent; D000328:Adult; D000818:Animals; D016587:Antimutagenic Agents; D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D011994:Recombinant Proteins; D012854:Sister Chromatid Exchange / Q000187:drug effects; D055815:Young Adult
D016587:Antimutagenic Agents; D000972:Antineoplastic Agents, Phytogenic; D009153:Mutagens; D011994:Recombinant Proteins; D004921:Erythropoietin; D000077146:Irinotecan; D002166:Camptothecin