الفهرس 
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Abstract
Fluorouracil is widely used in the world as an anticancer drug and clinically commonly used for the treatment of solid tumours of the breast, ovaries, head, neck, gastrointestinal and colorectal tumours.
Hence, the present study was constructed for the evaluation and assessment of the expected toxicity effects of 5 - fluorouracil on bone marrow chromosomes and testes of adult male albino mice (Mus musculus) and to investigate the protective role of vitamin C against geno-and pathogenic impacts of this drug.
In order to achieve these intended goals, the experimental design was carried out in the following manner: sixty adult mice were used in the present study. They were allocated into six equal groups. The first group served as control group and each animal was injected intraperitoneally (i.p.) with the solvent of the drug (0.9 % NaCl) and the second and third groups were 5-FU treated groups. Each animal from these groups was injected (i.p.) with 80 mg/kg b.wt. of 5-FU in every other day for two and four weeks, respectively. While, each animal from the fourth and fifth groups was injected (i.p.) with 5-FU in every other day in addition to daily injection (i.p.) with vitamin C (12 mg/kg b.wt.) for two and four weeks, respectively. The animals of sixth group were injected (i.p.) with 12 mg/kg b.wt. of vitamin C for four weeks.
Therefore, the present investigation included chromosomal examination of both control and treated groups of mice in addition to histological examination of the testes in control and experimental groups.
The results of the present study can be summarized as follows:
Cytogenetical results:
The frequency of total chromosomal aberrations, in bone marrow cells, was significantly increased (P<0.001) in both periods (two and four weeks) of treatment with 5-FU. These structural aberrations were constituted of chromosomal and chromatid abnormalities. According to decreasing records, the former structural aberrations were included centromeric attenuation, ring chromosome, end to end association, chromosome gap, chromatid gap, centric fusion, beaded chromosomes and sticky chromosomes according to decreasing records. Whilst, the second once of 5-FU induced aberrations were involved deletion and fragment. Such results reflected the clastogenic effect of 5-FU on chromosomes of mouse bone marrow cells. While, the frequency of chromosomal aberrations after administration of vitamin C in addition to 5-FU was significantly decreased (P˂0.05) in comparable with 5-FU treated groups, reflecting a protective role of vitamin C on bone marrow cells of mice.
Moreover, the results of this study recorded decrease in the mitotic index of bone marrow cells after administration of 5-FU for two and four weeks, but after administration of 5-FU in addition to vitamin C for two and four weeks, there were a noticeable elevation in the mitotic index of bone marrow cells.
Such results also reflected the expected inhibition role of cytostatic agent ’’5-FU’’ on mitotic rate of bone marrow and the regulatory role of vitamin C on cell division stages.
Histological results:
At light microscopical level, histological examination of the testes of treated mice exhibited many histopathological changes. These changes elaborated in both seminiferous tubules and interstitial tissue of the testes of treated mice compared with the control. These changes were marked severe degenerative features of the seminiferous tubules and their spermatogenic cells, rupture of basement membrane of some seminiferous tubules, disattachment and disorganization of the testicular tissue causing wide spaces between tubules, gradual degenerative features in the testicular tissue involved mainly vacuolar degeneration and ended by necrosis of spermatogonia and primary spermatocytes being concomitance with nuclear lesions reflected as pyknosis and karyolysis, degenerative alterations of seminiferous tubules with maturation arrest in the late stage spermatids, damage and hypoplasia of leydig cells and interstitial tissue and Congestion of blood vessels represented by dilation blood vessels besides the detected haemorrhagic areas in the intertubular spaces.
Some seminiferous tubules partially restored their spermatogenesis and the spermatogenic cells partially restored their normal configuration after administration of vitamin C in addition to 5-FU for two and four weeks, reflecting a protective effect of vitamin C.
In conclusion, the foregoing results referred clearly to that 5-fluorouracil had produced deleterious impacts on bone marrow chromosomes and testes of treated mice. Whereas, the results of treatments with vitamin C indicated that it statistically significantly decreases the number of chromosomal aberrations induced by 5-FU, but it can’t completely protect cells from damage. In addition, some seminiferous tubules partially restored their spermatogenesis after administration of vitamin C concurrently with 5-FU for both periods of treatment. So, the study suggested that vitamin C may be a potential protective agent against the toxicity of 5-FU, but further research with both normal and cancer cells are needed to clarify this point.