Some Inhibitors of Deamination of 9-β-d-Arabinofuranosyladenine and 9-β-d-Xylofuranosyladenine by Blood and Neoplasms of Experimental Animals and Humans

Earlier studies concerning the relationship between adenosine deaminase and the response of ascites tumors in mice to analogs of adenosine were extended to subcutaneous mouse tumors. A tumor with relatively high adenosine deaminase activity, Sarcoma 180, was relatively unresponsive to 9-β-d-arabinofuranosyladenine (Ara-A) and 9-β-d-xylofuranosyladenine (Xyl-A). Tumors with lower deaminase content, Carcinoma 1025 and Ridgeway osteogenic sarcoma, were more responsive. Loss of Xyl-A and Ara-A due to deamination in mouse blood was studied under the influence of inhibitors. Several nucleosides were good inhibitors in vitro but had no useful effects in vivo . Agents preventing entry of the deaminase substrates into blood cells were effective in vivo . The most prolonged effects were obtained with 4-ethanolisopropanolamino-2-7-di(2′-methylmorpholino)-6-phenylpteridine. Levels of adenosine deaminase in the blood of mice, rats, monkeys, and humans were determined. A survey was also made of adenosine deaminase levels in 41 human tumor samples.