Purine Deoxyribonucleoside Induced Hepatotoxicity in the Mouse
Although treatment of mice with the adenosine deaminase (ADA) inhibitor 2f-deoxycoformycin (dCf) in combination with 2′-deoxyadenosine (AdR) resulted in bone marrow toxicity, death was attributable to acute hepatic dysfunction.1 The toxic effects of AdR in ADA inhibited cells have been attributed to several different processes including inhibition of ribonucleotide reductase by deoxyadenosine triphosphate (dATP)2 and AdR inhibiton of S-adenosylhomocysteine (SAH) hydrolase. 3We have explored these two biochemical aspects in the livers of mice receiving AdR/dCf combinations, and report here deoxynucleoside triphosphate (dNTP) levels and preliminary measurements of perturbations in liver SAH and S-adenosylmethionine (SAM) following such treatment.
KeywordsAdenosine Deaminase Ribonucleotide Reductase Deoxynucleoside Triphosphate Bone Marrow Toxicity Potassium Bicarbonate
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- 2.K.R. Harrap and R.M. Paine, Use of a regulatory effector as a potential antitumour agent, Characterisation and Treatment of Human Tumours 4: 239 (1978) Excerpta Medica.Google Scholar