losartan-potassium and Leukemia-P388

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.

Topics: Adolescent; Adult; Animals; Antimutagenic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Cell Proliferation; Cells, Cultured; Erythropoietin; Humans; In Vitro Techniques; Irinotecan; Leukemia P388; Lymphocytes; Mice; Mitosis; Mutagens; Recombinant Proteins; Sister Chromatid Exchange; Young Adult

Erythropoietin (EPO) is a glycoprotein which has a main property, erythropoiesis, but its range of action in the human body is very wide. It has been suggested that EPO acts cytoprotectively for many cell lines against many toxic causes in vitro and in vivo. Our aim was to study the action of EPO on DNA of two cell types, human lymphocytes in vitro and on P388 ascites tumor cells inoculated in BDF1 mice in the presence and absence of the genotoxic agent mitomycin C (MMC).. The sister chromatid exchange (SCE) assay was used as it is a very sensitive, simple and rapid method for detecting DNA damage. Proliferation rate indices (PRI) and mitotic indices (MI) were also counted.. EPO did not alter the SCE level when it acted alone on both cell lines. MMC as a potent genotoxic agent increased SCE levels in vitro and in vivo. EPO used in combination with MMC significantly decreased SCE levels and increased PRI and MI values induced by MMC alone both in vitro and in vivo.. EPO acts protectively against the genotoxic potential of MMC, and this action may have clinical implications.

Topics: Adolescent; Adult; Animals; Cells, Cultured; Cytogenetic Analysis; Drug Combinations; Erythropoietin; Humans; Leukemia P388; Lymphocytes; Mice; Mitomycin; Recombinant Proteins; Sister Chromatid Exchange; Young Adult