ABSTRACT
Background: Methotrexate is an antineoplastic, antipsoriatic and antirheumatic agent belongs to the group of antimetabolites and inhibits folic acid metabolism
Materials and methods: To investigate its possible effect, sixty male mice were randomly assigned to one of four groups [one control and three treated groups with different doses of methotrexate]. Mice of groups 1, 2 and 3 were intraperitoneally injected with 2.5, 5 and 10 mg /kg b.wt. methotrexate respectively. All the control and treated animals were sacrificed at 24, 48 and 72 hour by cervical dislocation post treatment
Results: Micronucleus assay results showed that methotrexate treatment induced genotoxicity in bone marrow cells, the number of micronucleated polychromatic erythrocytes [MNPCEs] and the ratio of polychromatic erythrocytes / normochromatic erythrocytes was gradually increased significantly [P < 0.001] by increasing dose and time of treatment in methotrexate treated groups in comparison with the control group. An analysis of randomly amplified polymorphism DNA-polymerase chain reaction [RAPD-PCR] showed different ranges of DNA modifications in the treated groups after 24, 48 and 72 hour of treatment in comparison with the control group. Results of this study indicate that methotrexate treatment induced cytotoxic and genotoxic effect on bone marrow cells and DNA content of male albino mice even after a low dose and single treatment
Conclusion: Therefore, the therapeutic uses of methotrexate should be restricted to a very narrow range border
ABSTRACT
Aim of the work: Methotrexate [MTX], a structural analogue of folic acid, is an antineoplastic and antirheumatic agent which is used in a variety of clinical schedules and combination therapy regimens in man
Material and methods: Sixty mice of nearly the same age were randomly categorized into four groups [one control and three treated groups with different doses of methotrexate]. Mice of the treated groups 1, 2 and 3 were intraperitoneally injected with a single dose of methotrexate [2.5, 5 or 10 mg/kg b. wt. respectively] at the first day of the experiment. All the control and the treated animals were sacrificed after 24, 48 or 72 hour by cervical dislocation post treatment
Results: Methotrexate treatment induced structural and numerical chromosomal aberrations in male mice bone marrow cells which were significantly increased [P< 0.001] by dose and time. Structural aberrations were chromosomal gap, fragment, break, centromeric attenuation, deletion, centric fusion, ring formation, end to end association and beaded chromosomes. Numerical aberration was polyploidy. Also, methotrexate treatment decreased the mitotic index in bone marrow cells of all the treated mice in comparison with the control group by increasing dose and time of treatment. Comet assay results indicated that treatment with methotrexate significantly increased [P< 0.001] DNA damage in the blood leukocytes in dose and time dependent manner
Conclusion: It can be concluded that methotrexate induced genetic damage on the chromosomes and DNA content of male albino mice even after single treatment with low doses
ABSTRACT
Background: mitomycin-C [MC] is an anti-cancer drug against several tumor types, including colon, breast and head and neck. In this demonstration, the genotoxic effects of mitomycin-C on DNA content and testicular tissue of male albino mice Mus musculus were studied.
Materials and Methods: mitomycin-C treated animal was injected intrapretonialy with tested doses of mitomycin-C single time at the first day of the experiment. Comet assay was used to detect the DNA damage in mice lymphocytes and the mean of total comet score was increased by dose and time among all treated groups
Results: The histological alterations caused in the testis of mice after mitomycin-C treatment displayed variable changes in both the seminiferous tubules and the interstitial tissue. Changes in seminiferous tubules were represented by hypoplasia of the germinal epithelium and spermatogenic arrest at various stages of spermatogenesis. The most prominent changes reported in the intertubular tissue were represented by the presence of a homogeneous and intensely eosinophilic ground substance in the interstitial areas, congestion of blood vessels as well as haemorrhage. The histological changes were also significantly increased by time and dose