Abstract
The DHL-9 wild type cell line is a human histiocytic lymphoma naturally devoided of deoxyadenosine deaminase activity. From this cell line a mutant, DHL-9, dAR-2, resistant to high concentrations of deoxyadenosine has been selected. To be cytotoxic deoxyadenosine has to be converted to the corresponding deoxyribonucleoside triphosphate, which is an inhibitor of ribonucleotide reductase. In this study we tested if the high resistance of DHL-9,dAR-2 to deoxyadenosine was due to either a higher level of ribonucleotide reductase or to an alteration of the structure of the nucleotide binding subunit, M1 of ribonucleotide reductase. The mutant was found to have a two to five times higher ribonucleotide reductase activity than the wild type in crude cell extracts. The mutant activity appeared to be as sensitive to dATP inhibition as the wild type enzyme. By SDS-gel electrophoresis followed by immunoblotting it was found that the M1-subunit level was 2-3-fold higher in the dAR-2 extracts than in the wild type. This increased protein M1-level may well explain the 10-20-fold higher resistance to deoxyadenosine of the dAR-2 cell line, but the reason for increased M1-production remains to be clarified.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dahbo, Y., Carson, D. & Eriksson, S. INCREASED LEVEL OF RIBONUCLEOTIDE REDUCTASE IN DEOXY ADENOSINE RESISTANT ADENOSINE DEAMINASE DEFICIENT HUMAN HISTIOCYTIC LYMPHOMA CELLS: 44. Pediatr Res 19, 751 (1985). https://doi.org/10.1203/00006450-198507000-00064
Issue Date:
DOI: https://doi.org/10.1203/00006450-198507000-00064