PMID: 3754453Mar 1, 1986Paper

The differential cytotoxicity of RSU 1069: cell survival studies indicating interaction with DNA as a possible mode of action

British Journal of Cancer
I J StratfordA R Silver

Abstract

The hypoxic cell radiosensitizer RSU 1069 (1-(2-nitro-1-imidazolyl)-3-(1-aziridinyl)-2-propanol) shows, on a concentration basis, a 100-fold greater toxicity towards hypoxic relative to aerobic cells. This toxicity is substantially greater than that of misonidazole, a compound of similar electron affinity. Reductive processes are important for hypoxic toxicity; this is demonstrated by the fact that misonidazole, in excess, can protect against the hypoxic but not aerobic toxicity of RSU 1069. The importance of the interaction of RSU 1069 with DNA, suggested initially by molecular studies, is supported by the fact that cells containing 5-bromodeoxyuridine (5-BUdR) incorporated into their DNA show greater sensitivity towards the lethal effects of RSU 1069 both in air and nitrogen, compared to cells not treated with 5-BUdR. Experiments with RSU 1069 and 3-aminobenzamide (3-AB) show the latter compound to potentiate aerobic toxicity, consistent with monofunctional alkylation by RSU 1069. In contrast, 3-AB has no effect on the hypoxic cytotoxicity of RSU 1069, which would be predicted if RSU 1069 is functioning as a bifunctional agent under these conditions. It is our contention that in air, RSU 1069 functions as a typical monofuncti...Continue Reading

Citations

Apr 1, 1988·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·J WallingM A Stephens
Apr 1, 1991·International Journal of Radiation Biology·G J van den AardwegA B Nethersell
Aug 1, 1987·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·K R AustenE M Fielden
Jul 5, 2005·Expert Opinion on Investigational Drugs·R M Phillips
Jan 1, 1988·Drug Metabolism Reviews·G L Kedderis, G T Miwa
Feb 1, 1995·Mutation Research·D W FairbairnK L O'Neill
May 1, 1989·International Journal of Radiation Oncology, Biology, Physics·M Guichard

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