Enzymatic Deamination of Deoxyadenylic and Adenylic Acids by Normal and Cancerous Rat Liver Tissues23

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Abstract
To obtain information of the possible role of the enzymatic deamination of 5′-deoxyadenylic (dAMP) and 5′-adenylic acids (AMP) in rat liver carcinogenesis, the process was studied by a combination of polarographic, spectrophotometric, and paper chromatographic methods on homogenates and isolated subcellular fractions of normal rat liver, cancerous liver, and Novikoff tumor. Mouse Sarcoma 180 was also included. Whereas the homogenates quickly deaminated both AMP and dAMP in all cases, none of the purified subcellular particulate fractions alone could deaminate these nucleotides. The combination of supernatant and cytoplasmic elements (mitochondria and microsomes) did deaminate AMP and dAMP. 5′-Deoxyinosinic acid (dIMP) or 5′-inosinic acid (IMP) was never found in liver or tumor preparations while deoxyadenosine (dA), deoxyinosine (dl), hypoxanthine (in dAMP deamination) and inosine (I), hypoxanthine (in AMP deamination) were detected. There was a sufficient parallel between dephosphorylation and deamination of both nucleotides to warrant the conclusion that the enzymatic deaminations of AMP and dAMP in rat liver and liver tumors are brought about by the action of two enzymes: a phosphatase in the subcellular granules and adenosine (A) deaminase in the supernatant. The reactions are dAMP→dA→dI and AMP→A→I. The more rapid deamination of both nucleotides by tumor tissue is not due to increased levels of nucleotide-deaminase activity in tumors, but solely to the greater cell number per unit of weight in tumor as against corresponding normal tissue. In 3′-methyl-4- dimethylaminoazobenzene (3′-Me-4-DAB) carcinogenesis, however, the increased rate of A deamination was found to be a reversible phenomenon pertaining to the metabolism of the dye.