Enhancement of the Dimethylnitrosamine Acute Effects in Rat Liver by Prior Treatment With Triton WR-1339

Abstract

Prior administration of Triton WR-1339 (tyloxapol, an anionic surfactant) to noninbred Sprague-Dawley male rats significantly enhanced the intensity of the necrogenic effect of dimethylnitrosamine (DMN) on the liver. This phenomenon was established by determination of NADP⁺-linked isocitrate dehydrogenase activity in the plasma and by histologic procedures. This enhancing effect was not due to an increase in the levels of DMN that reached the liver, because the content of DMN in the livers of Triton WR-1339-treated or untreated animals at 1 or 3 hours was not significantly different. Triton WR-1339 administration had no effect on DMN liver metabolism to formaldehyde or CO₂; in addition, the covalent binding of DMN metabolites to nucleic acids or proteins was not modified by pretreatment with Triton WR-1339. However, in vitro, high concentrations (1 mg/ml) of Triton WR-1339 decreased the intensity of these parameters. This effect disappeared when the concentration was lowered to 0.4 mg/ml. Results are compatible with the hypothesis that the potentiating effects of Triton WR-1339 on liver damage caused by DMN and other hepatotoxins were due to a modification of the response of liver cells to injury.