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The Synergistic Effect of Hypoglycemia and L-Asparaginase upon Transplantable Hepatomas of Varying Growth Rates¹

Department of Pathology, New York University, School of Medicine, New York, New York 10016

L-Asparaginase inhibits the growth of several animal and human tumors and delays the onset of mitotic activity that occurs in the residual liver following 70% hepatectomy. In the present study the effect of this agent upon DNA synthesis in Morris hepatomas of varying growth rates was determined. A single, small dose of L-asparaginase produced a prolonged inhibition of a very-slow-growing tumor, 9618A. The DNA synthesis of this tumor was also inhibited by 70% hepatectomy alone. Neither a fast-growing tumor, 3924A, nor an intermediate tumor, 9121, was affected by either procedure alone. However, when L-asparaginase administration was combined with 70% hepatectomy, a prolonged suppression of DNA synthesis of hepatoma 9121 ensued while that of hepatoma 3924 remained unaffected.

Seventy % hepatectomy of rats bearing hepatoma 9121 resulted in a severe and prolonged hypoglycemia. The inhibition of DNA synthesis of hepatoma 9121 induced by the combined procedure of 70% hepatectomy and enzyme administration was reversed by the administration of glucose. It would appear, therefore, that the hypoglycemia induced in hepatoma 9121-bearing rats by operation sensitizes the tumor to the effect of L-asparaginase.

¹ This work was supported by a Grant from the Ruth Estrin Goldberg Memorial and Grant BC-53 from the National Cancer Institute, NIH. This work was presented in part at the Hepatoma Symposium, Philadelphia, Pa., May 17 to 18, 1971.

² Career Scientist, Health Research Council of the City of New York.

³ USPHS Fellow in Experimental Pathology.

Received 2/10/72. Accepted 6/12/72.