Testicular cytotoxicity of intravenous procarbazine in rats

Although the testicular cytotoxicity of procarbazine has been evaluated in the rat, previous models have utilized routes other than the intravenous one, and have generally employed multiple-dose regimens. In this report, we describe testicular toxicity in the Sprague-Dawley rat following a single intravenous bolus of procarbazine (0-700 mg kg body weight), with necropsy 59 +/- 2 days later. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulation index and epididymal index. Effects of procarbazine on heart, lung, liver and kidney histology were evaluated qualitatively. Progressive dose-dependent testicular atrophy and oligospermia occurred at low and intermediate dosages of procarbazine. Marked testicular atrophy, oligospermia and germinal hypoplasia were observed at high dosages (500 and 700 mg kg-1 body weight). LD50 at day 59 for procarbazine appears to be approximately 600 mg kg-1 body weight using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage.