872 9 archive 2 disk0/00/00/08/72 2007-10-18 17:32:10 2007-10-31 23:34:20 2007-10-18 17:32:10 article show D‘Souza Urban J.A. dsouza@kb.usm.my Universiti Sains Malaysia, School of Medical Sciences, Dept. of Physiology pub R none 5-fluorouracil, sperm count, epididymis, physiology The antimetabolite, 5-fluorouracil is widely used in the treatment of cancers. Although its toxic effects on testis causing germinal epithelial sloughing, tubular atrophy and generation of multinucleated cells were reported, its effect on spermatogenesis has not been studied. Hence the present study was conducted to evaluate the effects of 5-fluorouracil on epididymal sperm count. Male Wistar rats were employed in the study (n=5 per group). The animals were injected (i.p) with five consecutive doses of 5-fluorouracil (10, 20, 30mg/kg b.w) at an interval of 24h and the control with 0.1ml-distilled water. Samples were obtained at 14, 35, 42 and 70 days after injection. Rats were sacrificed, a laparatomy was performed and epididymes were collected in 1ml phosphate buffered saline (pH 7.2), minced, filtered and stained with 1% aqueous eosin Y. An aliquot was taken in leucocyte pipette, diluted with phosphate buffered saline and sperm count was done as per the standard procedure. Data were analyzed by Mann Whitney U test. The results of this study revealed that 5-fluorouracil significantly decreased the sperm count in a dose- and time- dependent manner. 2003-01 published Malaysian Journal of Medical Sciences 10 1 School of Medical Sciences, Kubang Kerian, Universiti Sains Malaysia 43-45 TRUE 1394195X http://www.medic.usm.my/publication/mjms/ 1. Kovach J.S., Beart R.W. Cellular pharmacology of fluorinated pyrimidines in vivo in man. Invest New Drugs 1990; 7:13-25. 2. Ochuchida A., Furukawa A., Yoshida J., Watanabe M., Aruga F., Miwa Y. Micronucleus assays on 5-fluorouracil and 6-mercaptopurine with mouse peripheral blood reticulocytes. Mutat Res 1992; 139-143. 3. Narayana K., Urban D‘Souza J.A., Sanyal A.K., Rao K.P.S. 5-Fluorouracil (5-FU) induces the formation of giant cells and sloughing of seminiferous epithelium in the rat testis. Indian J Physiol Pharmacol 2000; 44:317-322. 4. D’Souza Urban J.A, Narayana K. Induction of seminiferous tubular atrophy by single dose of 5-fluorouracil(5-FU) in Wistar rats. Indian J Physiol Pharmacol 2001; 45: 87-94. 5. Russell L.D., Russell J.A. Short term morphological response of the rat testis to administration of five chemotherapeutic agents. Am J Anat 1991; 192: 142-168. 6. Takizawa S., Horii I. Endocrinological assessment of toxic effects on the male reproductive system in rats treated with 5-fluorouracil for 2 or 4 weeks. J Toxicol Sci 2002; 27: 49-56. 7. Vega S.G., Guzman P., Garcia l., Espinosa j de Nava C.C. Sperm shape abnormality and urine mutagenicity in mice treated with niclosamide. Mutat Res 1988; 204:269-276. 8. Wyrobek A.J., Gordon L.A., Burkhart J.G., Frnks M.W., Kapp Jr R.W., Letz G. An evaluation of the mouse sperm morphology test and other sperm tests in nonhuman mammals. Mutat Res 1983; 115: 1-72. 9. Lu C.C., Meistrich M.L. Cytotoxic effects of chemotherapeutic drugs on mouse testis cells. Cancer Res 1979; 39: 3575-3582. 10. Rai S.P., Vijayalaxmi K.K. Tamoxifen citrate induced sperm shape abnormalities in the in vivo mouse. Mutat Res 2001; 492: 1-6. 11. Morris S.M. The genetic toxicology of 5-fluoropyrimidines and 5-chlorouracil. Mutat Res 1993;297: 39-51. 12. Lonn U., Lonn S. Interaction between 5-fluorouracil and DNA of human colon adenocarcinoma. Cancer Res 1984; 44: 3414-3418.