cytogenetic effects of methotrexate and cytarabine alone and in combination on g1 and g2 cell cycle stages of leukemic molt-4 cell line in vitro

introduction: this study was performed to analyze chromosomal aletrations in g1 and g2 immortalizedmolt-4 cell line following treatment with methotrexate (mtx) and cytarabine (ara-c) alone or incombination. material and methods: molt-4 cells were cultured and manitained in rpmi-1640 supplementedwith fetal calf serum, antibiotics and l-gluthamine. cells were treated with ara-c and mtx with aconcentration of 100ãmol/l at g1 and 50ãmol/l at g2. one and half hour prior to harvesting, cell wereexposed to colcemid. (0.1ãg/ml find concentration). microscopic slides were prepared using standard1000).‚procedure. after staining with 5% giemsa, metaphase was evaluated using light microscope ( results: results indicate that ara-c and mtx, at a 100ãmol/l concentration, used for treatment of g1cells, increase the frequency of chromosomal type aberrations; although ara-c was more potent in aberrationinduction. the effect of combined treatment with ara-c and mtx on g1 cells was more than effect of eachdrug when used alone. the effect of these drugs on g2 cells with a concentration of 50ãmol/l was found to besignificantly different with that of controls (p<0.05). the frequency of chromatid type breaks induced by ara-cwas considerably higher than mtx. when these drugs were used in combination, the frequency of aberrationsincreased dramatically. conclusion: results indicate that both ara-c and mtx produce clastogenic effects on molt-4 cells.combination treatment with ara-c and mtx has an additive effect on g1-cells. but a synergistic effect wasfound when they were used for treatment of g2-cells. the reason for hypersensitivity of g2-cells to chemicalsmight be due to shorter repair time of lesions induced in dna, which are experessed as chromatid typeaberrations in the first mitosis.