William C. Dolowy

L-Asparaginase:Toxicity to Normal and Leukemic Human Lymphocytes

Quantitative in vitro tests showed that purified preparations of L-asparaginase from Escherichia coli were more toxic to blood lymphocytes from 12 of 15 patients with chronic lymphocytic leukemia than to lymphocytes from 25 persons with normal hemograms. Incubation for 7 days with 10 units per milliliter killed, on the average, 77 percent of leukemic and 34 percent of normal lymphocytes. The reagent produced appreciable toxicity to leukemic lymphocytes after 2 days of incubation.

Studies of Germfree Animals I. Response of Mice to Infection With Influenza A Virus.

Summary Germfree mice were found to be more susceptible than conventional mice to mouse-adapted influenza A strain PR8, although the difference in susceptibility is small. Work with more precise dosage methods is indicated to ascertain the nature of the difference. At 21 days after infection, the predominant leukocytic response in GF lungs was lymphocytic infiltration, while conventional mice responded with lymphocytes, polymorphonuclear leukocytes, and macro-phages. Gamma2 globulin was not detected by IE prior to infection either in GF mice or in 20 of 23 GF mice at 3 weeks after infection. HI antibody was not detected in GF mice before and after infection, but was detected in conventional mice after infection. Addendum. Since the submission of this paper, we have been able to elicit HI antibody production in germfree mice after intra-peritoneal inoculation of five LD50 of live PR8 virus.

Toxicity of L-Asparaginase to Resistant and Susceptible Lymphoma Cells in vitro

Summary and conclusions The 6C3HED lymphoma which is susceptible to E. coli L-Ase in vivo, is also susceptible to E. coli L-Ase in vitro. The 6C3HED-ECLAR1 lymphoma which is resistant to E. coli L-Ase in vivo is also resistant to E. coli L-Ase in vitro. At 2 days of incubation, these cells respond to L-Ase concentrations of 1,000 to 10,000 fold of that needed to exert a cytotoxic effect upon the susceptible cell line. Spleen cells are approximately as resistant as the 6C3HED-ECLAR1 lymphoma. Thymus cells are more susceptible than spleen cells, but more resistant than the susceptible tumor cell line.