THE EFFECT OF 3'-DEOXYADENOSINE N-1-OXIDE ON GROWTH IN-VITRO AND IN-VIVO ON EHRLICH ASCITES TUMOR AND ON A HUMAN SQUAMOUS LUNG-CELL CARCINOMA XENOGRAFT IN NUDE-MICE

The effect of 3'-deoxyadenosine N-1-oxide (3'-dANO) on Ehrlich ascites tumor and a human squamous lung cell carcinoma was investigated. The 3'-dANO concentration that inhibited the cell growth 50% (IC50) in Ehr lich ascites tumor cells in vitro was 0.15 mM, and the killing efficie ncy concentration (concentration of the drug that kills all cells) was 1 mM. By simultaneous administration of 3'-dANO and the adenosine dea minase inhibitor erythro-9-(2-hydroxyl-3-nonyl) adenine (EHNA), the IC 50 of 3'-dANO was unchanged, but the killing efficiency concentration of 3'-dANO was reduced to 0.3 mM. When mice bearing Ehrlich ascites tu mor were treated i.p. with 3'-dANO doses of 200 mg/kg daily for 4 days , the mean increased life span (ILS) was 200%. 3'-dANO in combination with EHNA did not further increase the life span of The tumor-bearing mice. The specific growth delay (SGD) of the Ehrlich tumor and of a hu man squamous lung cell carcinoma growing subcutaneously in 3'-dANO-tre ated mice were calculated from Gomperts tumor growth curves. The Ehrli ch tumor-bearing mice received 3'-dANO i.p, at doses of 250 mg/kg dail y for 4 days, and the nude mice bearing human carcinoma received 3'-dA NO i.p. at doses of 225 mg/kg daily for 5 days. The SGD for the invest igated tumors were calculated to be 1.0 and 1.1, respectively.