The British Journal of Radiology, Vol 48, Issue 567 209-220, Copyright © 1975 by British Institute of Radiology

ARTICLES

In vivo testing of hypoxic radiosensitizers using the KHT murine tumour assayed by the lung-colony technique

AM Rauth and K Kaufman

The KHT transplantable tumour of C3H mice has been used as a model tumour for the invivo study of hypoxic cell sensitizers. Eleven sensitizers comprising four nitrofuran five nitrobenzene and two nitroimidazole derivatives, which have been shown to be effective on hypoxic mammalian cells in vitro, have been investigated. Two of these compounds, metronidazole (2-methyl-5-nitroimidazole-1 ethanol) and tinidazole (ethyl [2-(2'-methyl-5'-nitro-1'-imidazolyl) ehtyl] sulfone), showed signs of hypoxic cell-sensitization in vivo when given systemically by intraperitoneal injections. In addition, preliminary testing of the nitrobenzene NDPP (P-NITRO-3-DIMETHYL-PROPRIOPHENONE HYDROCHLORIDE) INDICATED THAT WHEN IT WAS INJECTED DIRECTLY INTO THE TUMOUR AND IRRADIATION WAS COMPLETED WITHIN TEN MINUTES AFTER INJECTION, APPRECIABLE SENSITIZATION WAS OBTAINED. More detailed studies indicated that both metronidazole at 1,500 mg/kg and tinidazole at 750 mg/kg given intraperitoneally gave an enhancement ratio of 1-5 for a chronically hyopix cell population in this solid tumour in air-breathing mice. Measures of plasma levels of metronidazole and enhancement ratios obtained in the present in vivo system seem in relative agreement with the in vitro and in vivo results of others.

This article has been cited by other articles:

				A. Wouters, B. Pauwels, F. Lardon, and J. B. Vermorken Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions Oncologist, June 1, 2007; 12(6): 690 - 712. [Abstract] [Full Text] [PDF]

				R. Sutherland Cell and environment interactions in tumor microregions: the multicell spheroid model Science, April 8, 1988; 240(4849): 177 - 184. [Abstract] [PDF]