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Detection of Endotoxin in Commercial L-Asparaginase Preparations by Complement Fixation and Separation by Chromatography

Institute of Medical Microbiology, J. Gutenberg University, D-65 Mainz, Germany [M. L.]; Microbiological Associates, Inc., Bethesda, Maryland 20014 [S. V.]; and Viral Leukemia and Lymphoma Branch, Laboratory of Cell Biology [S. S.], Biology Branch [T. B.], and Drug Research and Development, Chemotherapy [A. G.], National Cancer Institute, Bethesda, Maryland 20014

Of 15 L-asparaginase preparations tested, 13 inhibited whole human serum complement; the inhibitory effect ranged from 12 to 45%. We have partially characterized the anticomplementary activity in one of the L-asparaginase preparations. The anticomplementary activity was separable from the L-asparaginase activity on Sephadex G-200. Fractions containing L-asparaginase had no effect either on whole human serum complement or on human serum C1, the first component of complement; these fractions were therapeutic in leukemic mice. Fractions containing the anticomplementary activity had no significant therapeutic effect in leukemic mice. L-asparaginase and the anticomplementary factor are antigenically distinct, and the anticomplementary factor was shown to be antigenically related to Escherichia coli lipopolysaccharide (endotoxin).

¹ Guest worker in the Biology Branch, National Cancer Institute. Supported by the Deutsche Forschungsgemeinschaft Lo 188/1.

² To whom reprint requests should be sent, at National Cancer Institute, Building 37, Room 2B15, Bethesda, Md. 20014.

Received 5/31/72. Accepted 7/12/72.

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