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.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008920:Misonidazole / Q000633:toxicity; D009422:Nervous System Diseases / Q000139:chemically induced*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*
D011838:Radiation-Sensitizing Agents; D008920:Misonidazole; D005966:Glucuronidase