The effect of 3′-deoxyadenosine N1 -oxide on growth in vitro and in vivo on Ehrlich ascites tumor and on a human squamous lung cell carcinoma xenograft in nude mice

Abstract

The effect of 3′-deoxyadenosine N1 -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 Ehrlich ascites tumor cells in vitro was 0.15 mM, and the killing efficiency concentration (concentration of the drug that kills all cells) was 1 mM. By simultaneous administration of 3′-dANO and the adenosine deaminase inhibitor erythro-9-(2-hydroxyl-3-nonyl) adenine (EHNA), the IC50 of 3′-dANO was unchanged, but the killing efficiency concentration of 3′-dANO was reduced to 0.3 mM. When mice bearing Ehrlich ascites tumor 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 human squamous lung cell carcinoma growing subcutaneously in 3′-dANO-treated mice were calculated from Gomperts tumor growth curves. The Ehrlich tumor-bearing mice received 3′-dANO i.p. at doses of 250 mg/kg daily for 4 days, and the nude mice bearing human carcinoma received 3′-dANO i.p. at doses of 225 mg/kg daily for 5 days. The SGD for the investigated tumors were calculated to be 1.0 and 1.1, respectively.