The Influence of Thiols on the Pre-irradiation Incubation Effect of Nitroimidazoles in E. Coli Cells

Author： Anderson Robert F.   Patel Kantilal B.   Stratford Michael R.L.  

Publisher： Informa Healthcare

ISSN： 1362-3095

Source： International Journal of Radiation Biology, Vol.48, Iss.4, 1985-10, pp. : 485-494

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Abstract

The increase in the degree of radiosensitization of Escherichia coli cells following prolonged pre-irradiation incubation with nitroimidazoles is not correlated with the loss of intracellular non-protein thiols (NPSH) alone. The rates of reduction of the nitro compounds and the NPSH removal do not show strong dependencies on the lipophilicities of the nitroimidazoles whereas the highly lipophilic compound RGW-609 effects an increase in radiosensitization in a much shorter incubation time than the other nitroimidazoles. Exogenous dithiothreitol (DTT) increased the rate of reduction of misonidazole in the cells but did not alter the fraction converted to the amine. Added DTT (0·15 mmol dm−3) completely protected against the pre-irradiation incubation effect of misonidazole (2·5 mmol dm−3) when added at the start of the incubation but only partially protected when added before irradiation. It is suggested that NPSH can intercept metabolite(s) (or their precursors) of nitroimidazoles which can potentiate cell killing by radiation.

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