Effect of 2'-deoxycoformycin infusion on S-adenosylhomocysteine hydrolase and the amount of S-adenosylhomocysteine and related compounds in tissues of mice.

Mice were given constant infusions of the adenosine deaminase inhibitor, 2'-deoxycoformycin, by i.p. implantation of microosmotic pumps, delivering the compound at a rate of 0.16 mg hr-1 kg-1. In accordance with published data, we observed that adenosine deaminase in most tissues was nearly completely inhibited. In addition, the S-adenosylhomocysteine hydrolase activity decreased slowly and showed a half-life in liver of about 4 hr. The rate and extent of the inactivation were highest in spleen. The amounts of adenosine, 2'-deoxyadenosine, S-adenosylhomocysteine, and S-adenosylmethionine were determined in treated animals and control animals. The tissue levels of adenosine and, to a lesser degree, S-adenosylhomocysteine and S-adenosylmethionine were critically dependent on the procedure used for processing the tissues. Lowest concentrations were observed when the organs were frozen in situ by liquid nitrogen. Treatment with 2'-deoxycoformycin induced no or a moderate increase in tissue content of adenosine and S-adenosylhomocysteine, whereas the amount of 2'-deoxyadenosine increased markedly, especially in spleen and thymus. 2'-Deoxycoformycin treatment caused an increase in adenosine and 2'-deoxyadenosine, but not S-adenosylhomocysteine, in serum of mice.