Neurotoxicity of radiation sensitizers in the mouse

The neurotoxicity of a homologous series of 1-substituted, 2-nitroimidazole compounds, synthesized in this laboratory, has been studied in mice. This involves measurement of the enzyme beta-glucuronidase in the distal sciatic, tibial and common peroneal nerves. The amount of compound required to give a known neurotoxic response, in terms of elevated beta-glucuronidase (arbitrarily set at 60% increase) has been determined. A correlation between increased number of methylene groups (N) in the side chain and neurotoxicity has been shown. A correlation between increased neurotoxicity and effective octanol; water coefficient, at pH 7.4, was also established. A more soluble version of the n = 4 member of the homologous series, that is the compound RSU 1047 (NSC 328897), and misonidazole also fit this correlation of partition coefficient and dose.