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Characterization of an Adenosine Deaminase-deficient Human Histiocytic Lymphoma Cell Line (DHL-9) and Selection of Mutants Deficient in Adenosine Kinase and Deoxycytidine Kinase¹

Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, California 92037 [M. K., N. K., D. A. C.], and Department of Internal Medicine, Human Purine Research Center, University of Michigan, Ann Arbor, Michigan 48109 [P. E. D.]

The association of adenosine deaminase (ADA) deficiency with immunodeficiency disease has emphasized the importance of this purine metabolic enzyme for human lymphocyte growth and function. This report describes the natural occurrence of ADA deficiency in a human histiocytic lymphoma cell line, DHL-9. The minimal ADA activity in DHL-9 extracts, 0.028 nmol/min/mg protein, was less than 50% of the activity in two B-lymphoblastoid cell lines from ADA-deficient patients and was resistant to the potent ADA inhibitor deoxycoformycin. A sensitive radioimmunoassay failed to detect immunoreactive ADA in DHL-9 cells. Moreover, in DHL-9 cells, deoxycoformycin did not augment either the growth-inhibitory effects of adenosine and deoxyadenosine or the accumulation of deoxyadenosine triphosphate from deoxyadenosine. When compared to six other human hematopoietic cell lines, DHL-9 had 5.6-fold-higher levels of adenosylhomocysteinase. Chromosome 20, which bears the structural gene for ADA and adenosylhomocysteinase, was diploid and had a normal Giemsa banding pattern. The parental DHL-9 cell line was used for the selection and cloning of secondary mutants deficient in deoxycytidine kinase and adenosine kinase.

¹ This work was supported by Grant GM 23200 from the NIH and Grants CA 31497 and CA 26284 from the National Cancer Institute.

² Present address: Department of Medicine and Physical Therapy, University of Tokyo, Tokyo, Japan.

³ To whom requests for reprints should be addressed, at Department of Basic and Clinical Research, BCR4, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, Calif. 92037.

Received 12/ 1/82. Accepted 3/ 8/83.