Phagolysosomal alterations induced by unleaded gasoline in epithelial cells of the proximal convoluted tubules of male rats: effect of dose and treatment duration.

Short-term oral administration of unleaded gasoline to male rats reproduces the accumulation of phagolysosomes (hyaline droplets) in epithelial cells of the renal proximal convoluted tubules (PCT) observed following long-term inhalation of wholly volatilized gasoline. Phagolysosomes are partially composed of alpha 2u-globulin, a low-molecular-weight protein, unique to male rats. In this study, dose-dependent and chronologic alterations of phagolysosomes caused by gasoline were observed by transmission electron microscopy. Exposure to commercially available unleaded gasoline (0.4-2.0 ml/kg, po, once daily, 9 d) increased the number and size of phagolysosomes in epithelial cells of the PCT in male rat kidney. However, administration of 0.04 ml gasoline/kg or less was ineffective in inducing phagolysosomal accumulation. Subcellular analysis revealed that many of the phagolysosomes observed in treated rats (doses greater than 0.4 ml/kg) were angular and had cross-sectional diameters varying from 0.5 to 9 microns; in controls the majority of phagolysosomes were round and their diameter varied from 0.5 to 2.5 microns. Treatment of male rats with gasoline (2.0 ml/kg body weight, po, 1-9 d) caused a progressive increase in the number and size of phagolysosomes in PCT epithelial cells dependent on treatment duration. Alterations in phagolysosomal morphology and quantity occurred within 20 h following a single dose of gasoline, emphasizing that the process of phagolysosome accumulation is a dynamic phenomenon. Many of the enlarged phagolysosomes contained a condensed, crystalline core of greater electron density than the surrounding matrix. Furthermore, the rapid increase in abnormal, condensed contents in the phagolysosomes may indicate that a derangement of renal protein catabolism is the primary mechanism by which fuel hydrocarbons cause hyaline droplet nephropathy in male rats.