Toxic effect of L-asparaginase(NSC 109229, Merck Sharp & Dohme) on pancreas after single or repeated administration was studied in rabbits and rats. Rectal temperature was slightly eleva,ed in rabbits at one hour after intravenous administration of L-asparaginase with an interm iate dose. Serum amylase level was slightly lowered at 3 hours and elevated markedly at 24 hours fter ingle administration of L-asparaginase in rabbits. In rats serum amylase level was significant) deceased at one day after administration of L-asparaginase in a daily dose of 1000 iu/kg for 7 day , however, the amylase level was restored and then elevated at 14 days after treatment. The ratio o live and spleen weight to body weight were increased at one day after repeated L-asparaginase treat iient, but the ratio of pancreas was not changed in rats. Pancreatobiliary secretion was markedly decreased after repeated administration of L-asparaginase and the effect was sustained until 14 days after withdrawal of the treatment, however, the panc eatic enzyme contents were not changed. Microscopically acinar dissociation, a slight increase of vacuoles and a decrease of pyronophilic material were observed in 6 and 18 hours after single injection f Lasparaginase in the dose ranges of 2, 000 to 20, 000 iu/kg in rats. The ultrastructural alterations con-sisted of early dilation of rough endoplasmic reticulum and detachment of ribosoines. and ´ther.r ter only phagocytic autophagic vacuoles in acinar cells were seen at 48 to 72 hours after L-aparaginase injection.
By the above results it is to note that the toxicity of L-asparaginase to pancreas was not striking and felt that the pancreatic changes induced by L-asparaginase are due to the depletion of ce lular asparagine rather than bacterial contaminants in the preparation.
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