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العنوان
CYTOGENTICAL STUDIES OF
MITOMYCIN-C DRUG ON THE BONE
MARROW chrOMOSOMES OF MALE
ALBINO MICE Mus muscullus /
المؤلف
Husaiin, Ayman Mohammad Abdullllah.
هيئة الاعداد
باحث / Ayman Mohammad Abdullllah Husaiin
مشرف / Naglla Zaky Ibrahiim Ell--Allffy
مشرف / Mahmoud Fathy Mahmoud
مناقش / Mahmoud Fathy Mahmoud
تاريخ النشر
2014.
عدد الصفحات
413 P. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
علم الحيوان والطب البيطري
تاريخ الإجازة
1/1/2014
مكان الإجازة
جامعة عين شمس - كلية التربية - قسم علم الحيوان
الفهرس
Only 14 pages are availabe for public view

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Abstract

Mitomycin-C (MC) is a commonly used chemotherapeutic and immunosuppressive agent which is used in the treatment of wide range of cancers and autoimmune diseases. But unfortunately, mitomycin-C has a genotoxic effects on all body cells because it inhibits DNA replications in cancer cells as well as normal cells. The present investigation deals with the possible alterations that may occur in male albino mice Mus musculus after mitomycin-C treatment. This study has mainly aimed to evaluate the genotoxic effects of mitomycin-C on bone marrow chromosomes, DNA content and histopathological structure of testis in male albino mice Mus musculus.
A total number of sixty CD-1 male mice (16-17 weeks old and 26-30 g) were used in the current investigation. They were divided into five groups each group comprising 12 animals. The first group served as a control (injected with physiological saline solution 1ml/kg b.wt.) while the second group was treated with mitomycin-C (3 mg/kg b.wt. for one week), group (3) was treated with mitomycin-C (3 mg/kg b.wt. for two weeks), fourth group was treated with mitomycin-C (6 mg/kg b.wt. for one week) and fifth group was treated with mitomycin-C (6 mg/kg b.wt. for two weeks). Each mitomycin-C treated animal was intraperitoneally injected at the first day of the experiment.
The present study has been concerned with the observation of the chromosomal aberrations, assessment of genotoxic potential of mitomycin-C in bone marrow cells by micronucleus assay, recording the changes in the DNA bands, investigating DNA damage by Comet assay and examination of histological structure of the testis of control and treated animals.
The present study showed that the normal mouse chromosomes were 40 telocentric chromosomes. They were divided into five distinct groups; each contains the chromosomes of nearly equal lengths. Treatment with mitomycin-C to male mice induced structural and numerical chromosomal aberrations. Structural aberrations were deletion, fragment, chromatid gap, centric fusion, centromeric attenuation, ring and chromosomal gap. While, numerical aberration was polyploidy.
Chromosomal aberrations test showed that the mean of total aberrations was increased by dose and time and this increase in total aberrations was statistically high significant (P< 0.001) in all treated groups. results indicated also, that the highest rate of total aberrations was recorded in group 5 which treated with mitomycin-C (6mg/kg b.wt. for two weeks), while the lower rate of total aberrations was recorded in group 2 which treated with mitomycin-C (3mg/kg b.wt. for one week). In addition, results recorded that deletions and fragmentation had the highest rate of appearance among all types of aberrations.
In the present study micronucleus assay showed that treatment with mitomycin-C induces genotoxicity in mice bone marrow cell; the mean of polychromatic erythrocytes with micronucleus was increased by dose and this increase in polychromatic erythrocytes with micronucleus was statistically significant (P< 0.005) in group 3 treated with mitomycin-C (3mg/kg b.wt. for two weeks). While, this increase in polychromatic erythrocytes with micronucleus was statistically high significant (P< 0.001) in group 2 treated with mitomycin-C (3mg/kg b.wt. for one week), group 4 treated with mitomycin-C (6mg/kg b.wt. for one week), group 5 treated with mitomycin-C (6mg/kg b.wt. for two weeks). Also, cytotoxicity test (polychromatic erythrocytes: normochromatic erythrocytes) showed that treatment with mitomycin-C induces cytootoxicity in mice bone marrow cell; the mean of polychromatic erythrocytes: normochromatic erythrocytes was increased by dose and this increase was statistically highly significant (P< 0.001).
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 and these changes were represented by disappearance of some bands specially bands with low molecular size in the second group that treated with mitomycin-C (3 mg/kg b.wt. for one week), group (3) which treated with mitomycin-C (3 mg/kg b.wt. for two weeks) and in fourth group which treated with mitomycin-C (6 mg/kg b.wt. for one week).
In the present study, comet assay indicated that mitomycin-C treatment induced DNA damage in Peripheral blood lymphocytes of treated mice. The mean of total comet score was increased by dose and time. Statistical analysis showed that total comet score was significantly increased (P< 0.005) in group 2 that was treated with mitomycin-C (3 mg/kg b.wt. for one week) and total comet score showed highly significant increased (P< 0.001) in group (3) which was treated with mitomycin-C (3 mg/kg b.wt. for two weeks), fourth group that was treated with mitomycin-C (6 mg/kg b.wt. for one week) and fifth group which was treated with mitomycin-C (6 mg/kg b.wt. for two weeks).
On the light microscopic level, histological examination of the testis revealed histopathological changes. The severity of these lesions has been observed to be time and dose dependent. The main histopathological features induced in the testis of mice treated with mitomycin-C treatment were mainly alternations of the general architecture and maturation arrest at various stages of spermatogenesis. The mitomycin-C treatment induced changes included exfoliation of germ cells, formation of multinucleated giant cell, besides the various degrees of degeneration of germ cells. Most spermatocytes and spermatids appeared necrotized with highly vacuolated and pyknotic nuclei. In the intertubular tissue the most marked changes were haemorrhage, oedema and congestion of some blood vessels besides the various degrees of degeneration of Leyding cells.
In conclusion, these results reflect the injured effect of high dose and time of mitomycin-C on bone marrow chromosomes and DNA content as well as histological structure of the testis of treated mice with mitomycin-C. Therefore mitomycin-C should be used in very narrow range border.