CYTOGENTICAL STUDIES OF MITOMYCIN-C DRUG ON THE BONE MARROW CHROMOSOMES OF MALE ALBINO MICE Mus muscullus

Abstract

Mitomycin-C (MC)is an anti-cancer drug has a genotoxic effect on the bone marrow cells as this influence extends to the testicular tissue. The aim of this work is to study the genotoxic effecton bone marrow chromosomes, DNAcontent andtesticular tissue of male albino mice after mitomycin-C treatment.Sixtymale albino mice (16-17 weeks old and 26- 30 g.weight) were used in the present study and divided into five groups each group consists of 12 mice. The first group served as controlwas injected intrapretonialy with (physiological saline solution 1ml/kg b.wt.) while the second group was treated withmitomycin-C(3 mg/kg b.wt.) for one week,group (3) was treated with mitomycin-C (3 mg/kg b.wt.) for two weeks, group (4) was treated with mitomycin-C (6 mg/kg b.wt.) for one week andgroup (5) was treated with mitomycin-C (6 mg/kg b.wt.) for two weeks. Each mitomycin-Ctreated animal was intraperitoneally injected single time at the first day of the experiment. Resultsindicated that the treatingmale mouse with mitomycin-Cshowedchromosomal aberrations inbone marrow cellswhether structural aberrations and numerical aberration.Structural aberrationsweredeletion, fragmentation,chromatid gap,centric fusion, centromeric attenuation, ring and chromosomal gapping. While numerical aberration was polyploidy. Results of chromosomal aberrations indicated thattherates of total aberrations were increased by time and dose. Micronucleus assay illustrated that mitomycin-C treatment induced genotoxicity in bone marrow cells, and the rate of polychromatic erythrocytes with micronucleus was increased by dose. Also, cytotoxicity test showed that the polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs) ratio was increased by dose. In the current study, genetic changes among control and all treated groups have been studied according to RAPD-PCR analysis. Results indicated that mitomycin-C treatment induced genetic changes among control and all treated groups.Comet assay showed that mitomycin-C treatment induced DNA damage in mice lymphocytes and the mean of total comet score was increased by dose and time among all treated groups. The damage 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 andspermatogenic 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 in the interstitial tissue. The histological changes were also significantly increased by time and dose. Key words: Mitomycin-C, Chromosomes, Micronucleus,DNA, RAPD-PCR, Comet assay,Histopathology, Testis,Mic