FLOW CYTOMETRIC AND HISTOLOGICAL ASSESSMENT OF 1,2 3,4-DIEPOXYBUTANE TOXICITY ON MOUSE SPERMATOGENESIS/

The effects of diepoxybutane (DEB) on mouse reproductive cells have be en investigated by flow cytometric and histological description of tes ticular cell populations and alterations of sperm chromatin packaging. Mice were treated with single intraperitoneal injections of DEB, with doses ranging between 8.5 and 78 mg/kg (100-900 mu M), and were kille d after 7, 14, 21, 28, or 35 d. Dose-dependent reductions of tetraploi d cells, round spermatids, and elongated spermatids were detected at 7 , 21, and 28 d, respectively, reflecting cytotoxic damage on the diffe rentiating spermatogonia compartment. The dose necessary to reduce the number of differentiating spermatogonia to half the control value was estimated equal to 650 mu M or 55 mg/kg. Stem cells were not affected by this treatment. Histological section of seminiferous tubules showe d depletion of spermatids and reduction of the secondary spermatocyte layers. In addition, a high although not statistically significant fre quency of sperm with altered chromatin packaging was detected after DE B treatment. DEB is one of the key metabolites of butadiene, which is a compound of high environmental and occupational concern. These resul ts contribute to the assessment of the reproductive health impact or b utadiene in humans.