Low molecular weight immunosuppressive factors found in elevated amounts in cancer ascitic fluids of mice. 2. 1-Methyladenosine isolated from cancer ascitic fluids enhances Listeria infection in mice.

Abstract

The low molecular weight fraction (mol wt less than 1,000) of Ehrlich cancer ascitic fluid has been known to enhance Listeria infection in mice. Chemical characterization of the entities in this fraction revealed four purine and pyrimidine analogues, i.e. uric acid, uracil, pseudouridine and 1-methyladenosine (m1Ado). When the effect of each of these components was studied on Listeria infection in mice, only m1Ado markedly enhanced the infection and killed the mice within a short period. The optimal enhancement was obtained when m1Ado was given intravenously to mice 3-6 days before the infection at a concentration of between 1 and 100 micrograms/mouse. On the other hand, uric acid, uracil and pseudouridine failed to show such an enhancing effect. m1Ado inhibited macrophage accumulation in the peritoneal cavity of mice after an intraperitoneal injection of phytohemagglutinin. Although m1Ado did not show any inhibitory effect on the phagocytic and bactericidal activities of macrophages in vitro, peritoneal macrophages obtained from mice which received m1Ado 3 days ahead revealed impaired bactericidal activity, suggesting the migration of different cell populations from the bone marrow of m1Ado-receiving mice. The results may suggest that m1Ado is a major factor in tumor ascites causing, in small doses, an impairment of macrophage functioning as can be detected in tumor-bearing hosts.