Cancer Therapy Vol 4, page 131 damage in Wistar rat bone marrow cells. Mutat Res 419, 137-43. Arber N, Zajicek G, Nordenberg J and Zkelsidi Y (1991) Azathioprine treatment increases hepatocyte turnover. Gastroenetrology 101, 1083-1086. Au muller G, Schulze C and Viebahn C (1992) Intermediate filaments in Sertoli cells. Microsco Res Tech 20, 50-72. Baker HWG, Brindle J and Levine DS (1996) Protective effect of antioxidant on the impairment of sperm motility by activated polymorphonuclear leucocytes. Fetil Steril 65, 411-419. Baker GL, Kahl LE, Zee BC, Stolzer BL, Agarwal AK, Medsger TA Jr (1987) Malignancy following treatment of rheumatoid arthritis with cyclophosphamide. Long-term case-control follow-up study. Am J Med 83, 1-9. Blasiak J, Gloc E, Wozniak K, Mlynarski W, Stolarska M, Skorski T and Majsterek I (2002) Genotoxicity of idarubicin and its modulation by vitamins C and E and amifostine. Chem Biol Interact 140, 1-18. Bunn PA and Kelly K (1998) New chemotherapeutic agents prolong survival and improve quality of life in non-small cell lung cancer: a review of the literature and future directions. Clin Cancer Res 4, 1087-100. Cabrera G (2000) Effect of five dietary antimutagens on the genotoxicity of six mutagens in the microscreen prophageinduction assay. Environ Mol Mutagen 36, 206-20. Chaki SP, Srinivas M, Chaube SK (1999) Effect of cyclosporine on human sperm motility in vitro. Arch Androl 43, 215-220 Chen JS, Sensini C, Barelli M, Manca D and Menesinichen MG (2001) Ascorbic acid induced spectrin reorganization in bull epididymal spermatozoa. Cell Biol Toxicol 16, 77-82. Clark JM (1975) The mutagenicity of azathioprine in mice, Drosophila melanogaster and Neurospora crassa. Mutat Res 28, 87-99. Das UB, Mallich M, Debnath JM and Ghosh D (2002) Protective effect of ascorbic acid on cyclophosphamide-induced testicular gametogenic and androgenic disorders in male rats. Asian J Androl 4, 201-207. Dekretser DM, Burger HG and Forlune D (1972) Hormonal, Histological and chromosomal studies in adult male with testicular disorders. J Clin Endocrinol Metab 35, 392-401. Dhabhar BN, Malhotra H, Joseph R, Garde S, Bhasin S Sheth A and Advani SH (1993) Gonadal function in prepubertal boys following treatment for Hodgkin’s disease. Am J Pediat Hematol Oncol 15, 306-310. Dejaco C, Mittermaier C, Reinisch W, Gasche C, Waldhoer T, Strohmer H, Moser G (2001) Azathioprine treatment and male fertility in inflammatory bowel disease. Gastroenterology 121, 1048-53. Diasio RB and Lobuglio AF (1991) Immunomodulators: Immunosuppresive agents and Immunstimulants. In: Goodman GA, Rall TW Nies AS, Taylor P, editors. The pharmacological basis of theraputics. New York: Pergamon press pp, 1291-1308. Drury RAB, Wallington EA (1980) Carleton’s Histology Technique 5th ed Oxford, Newyork, Torento. Oxford University Press pp. 140-142. Ferguson LR, Whiteside G, Holdaway KM and Baguley BC (1996) Application of fluorescence in situ hybridisation to study the relationship between cytotoxicity, chromosome aberrations, and changes in chromosome number after treatment with the topoisomerase II inhibitor amsacrine. Environ Mol Mutagen 27, 255-262. Frago C (1991) Ascorbic acid protects against oxidative DNA damage in human sperm. Proc Nat Acad Sci USA 88, 11003-11006. Gajecka M, Kujawski LM, Gawecki J and Szyfter K (1999) The protective effect of vitamins C and E against B (a)P-induced
1998; Tavares et al, 1998; Pillanse et al, 2002; Blasiak et al, 2002). However, in our results vitamin C did not exert any protective effect on AZA induced structural chromosomal aberrations. Pillanse et al, 1990, found that ascorbic acid provide protection from cyclophosphamide induced teratogenic effect in mouse embryo, this protection is not associated with prevention of DNA strand breaks. Furthermore, vitamin C did not provide protection from genotoxic effect of toxophene, dichorovos and nitrosomorpholine compounds (Cabrera 2000; Robichova et al, 2004). Large dose of AZA associated with increased polyploidy cells. Motwani et al, 2000, suggested that cell with compremized G1 checkpoint in response to microtubule inhibitors enter S phase with 4n DNA, endoreduplicate and become polyploid cells. We suggested that large dose of AZA may act as microtubules inhibitors. Ferguson et al, 1996, observed increased number of polyploidy cells associated with high dose of amsacrine (antileukemic drug). Meanwhile, the use of small and large dose of this drug led to chromosomal fragments. Treatment of the rats with vitamin C 14 days following AZA treatment (150 mg/kg. b.wt.) caused a significant reduction in polyploidy cells. Motwani et al, 2000, showed that endoreduplication and polyploidation can prevented by inhibition of cycline-dependent kinase, resulted in the arrest of cells in pseudo G1 state and dramatic decrease in cells containing >4n DNA. Thomas et al, 2005, proved that vitamin C delay the accumulation and activation of cell cycle control kinases. Defects in cell cycle checkpoints can lead to chromosome abnormality, aneuploidy, and genomic instability, all of which can contribute to tumorigenesis (Lannutti et al, 2005; Vries et al, 2005). The antitumour effect of vitamin C has been proved (Roomi et al, 2005; Thomas et al, 2005). They proved that vitamin C transiently arrest cancer cell cycle progression in S phase and G (2)/M boundary by delaying the accumulation and activation of cell division control kinases/cycline complex. We suggesting that vitamin C provide genomic stability by preventing polyploidy In conclusion effort should be made to identify more careful design of non-toxic chemotherapy regimes. Vitamin C provided significant protection to the spermatogenic cells and provided genomic stability but did not protect the cells from structural chromosomal aberration. It may be used with other antioxidants for full protection of genetic material.
References Ahotupa M and Huhtaniemi I (1992) Impaired detoxification of reactive oxygen and consequent oxidative stress in experimentally criptorchid rat testis. Biol Reprod 46, 11141118. Annward J, Robinson J, Barrington JAF, Stephan MS and Ian DM (1990) Protection of spermatogenesis in rats from the cytotoxic Procarbazine by the Depot formulation of Zoladex a gonadotrophine-releasing hormone agonist. Cancer Res 50, 568-574. Antunes LM and Takahashi CS (1998) Effects of high doses of vitamins C and E against doxorubicin-induced chromosomal
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