Hepatic Lipidosis Associated with l-Asparaginase Treatment ∗

Abstract

Summary

Fatty infiltration of the liver following i.p. administration of partially-purified E. coli l-asparaginase was investigated using mice as experimental animals. Normal male C3H mice given varying dosage of low specific activity l-asparaginase over a 5-day period developed a marked hepatic lipidosis. Quantitative analyses and cytological studies confirmed this abnormal fat accumulation, in the form of triglycerides, compared with control animals given physiologic saline. By contrast, enzyme of high specific activity was not steatogenic to mice at the highest dose levels administered. Therefore, pure l-asparaginase per se does not appear to be steatogenic to mice. Quantitative analyses of liver tissues of a small group of l-asparaginase-treated leukemic patients showed marked hepatic lipidosis, regardless of amount or specific activity of enzyme administered. In fact, the severity of lipidosis seemed quite unrelated to the dose or purity of enzyme used. The limitations and possible implications of these findings are briefly discussed.