1,2-Dibromo-3-chloropropane (DBCP)-induced nuclear atypia in rat kidney

The reversibility of the nematocide 1,2-dibromo-3-chloropropane (DBCP)-induced renal injury was studied in adult male F344 rats. After a single dose of 200 mg DBCP/kg body weight, rats were sacrificed at 1, 3, 6, 9, 14, 28, and 196 days. Twenty-four hours after DBCP treatment, the animals showed signs of acute renal insufficiency, which, based on serum chemistry and urinalysis results, was reversed by the 14th day. Morphologic findings consisted of severe acute tubular necrosis, which was localized to the juxtamedullary cortex. The lesion was recognizable at 24 hrs and fully developed at 3 days post-exposure. The proximal convoluted tubuli were primarily affected, but there were also spotty necroses in distal convoluted tubuli and loops of Henle. Beginning regeneration was evident at 3 days post-exposure. Multiple mitoses, some of them abnormal, were seen. Four weeks after treatment some mitotic activity was still present, but the regeneration of the tubular epithelium was largely completed. There were several dilated, distorted tubuli lined with abnormal epithelial cells with large, hyperchromatic nuclei. Interstitial fibrosis was mild and there was no interstitial inflammation. Twenty-eight weeks post-exposure the nuclear atypia persisted in the tubular epithelium. Glomerular findings were minimal and consisted of focal hyperplasia of the epithelial cells of the parietal layer of Bowman's capsule and shrinking of the glomerular tufts at 4 weeks post-exposure. At 28 weeks post exposure only rare foci of glomerulosclerosis were seen. Epithelial cells of the renal pelvis showed minimal nuclear and cytoplasmic swelling 24 hrs after DBCP exposure. Urothelial atypia was not present. The results indicate that a single dose of DBCP is capable of producing nuclear atypia that persists in the renal tubuli beyond the regenerative phase. Follow-up of patients that have been chronically exposed to DBCP with periodic examination of urinary cytology is suggested.