Abstract
The toxicity of DA-125. a new anthracycline anticancer agent, on the male reproductive system was studied in Sprague-Dawley rats. Forty male rats were rando$m\ell$y assigned to Jour groups with ten rats in each group and given single intraveneous doses of DA-125 at dose levels of 0. 12.5. 25. and 50 mg/kg body weight. On day 56 after treatment the animals were allowed to mate. and their male reproductive Junctions and organs were examined in detail. Copulated females were sacrificed on day 20 of gestation for examination of embryo-fetal development. One out of ten rats in the 50 mg/kg group died on day 12 after treatment. Clinical signs such as emaciation. sedation, anorexia. swelling. dark material around eye. alopecia. and diarrhea were observed in the 25 and/or 50 mg/kg groups. Reduction in the body weight gain. decrease in the absolute weights of testes. epididymis and seminal vesicles. and/or decrease in the number of testicular sperm heads were also found. Although histopathological changes such as atrophy of seminiferous tubules. loss or decrease of spermatogenic cells. exfoliation of spermatogenic cells. vacuolization of Sertoli cells. decrease of sperm. and/or increase of necrotic spermatogenic cells in epididymal ducts were observed. no adverse effects on the motility and morphology of epididymal sperm. copulation index. fertility index. and embryo-fetal development were detected in the 25 and 50 mg/kg groups. There were no evidences of male reproductive toxicity in the 12.5 mg/kg group. These results show that single intravenouse doses of DA-125 produce significant dose-related testicular atrophy. histopathological changes. and oligozoospermia in rats and $LD_{10}$ for DA-125 appears to be 50 mg/kg body weight.
