Increased Incidence of Hepatic Foci and Nodules in Rats Given One or Two Doses of 1,2-Dibromoethane

Abstract

Livers of male Sprague-Dawley rats were evaluated for foci and nodules 90 days and 16 months after one or two oral doses of 1,2-dibromoethane (DBE). Rats (190 g) were given the following oral treatments. Controls received corn oil (2.5 ml/kg) at 0 and 24 hr. DBE × 1 received corn oil at 0 hr and 75 mg DBE/kg at 24 hr. DBE × 2 received 75 mg DBE/kg at 0 and 24 hr. All rats underwent a two-thirds partial hepatectomy at 28-29 hr, a one-third partial hepatectomy at 90 days, and were given 0.05% phenobarbital in drinking water for 4 months beginning at 1 yr. DBE was given to the DBE × 2 group twice within 24 hr because the compound is a hepatocyte mitogen. At 90 days, no appreciable changes were evident in any group. At 16 months, the incidence of nodules in the DBE × 2 group (25 of 41) was double that of the DBE × 1 group (12 of 38) ( p < 0.01) and triple that of the control group (6 of 34) ( p < 0,0001). Both the DBE × 1 and the DBE × 2 groups had higher incidences of eosinophilic foci, and also higher numbers, larger sizes, and larger areas of γ-glutamyltranspeptidase-positive foci than the control group. These results demonstrate for the first time that hepatocyte foci and nodules are initiated by limited exposure of animals to DBE.