DNA Damage and Radiosensitizers: M. luteus Sensitive Sites for Misonidazole-TAN Combination

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Abstract
TAN (2,2,6,6-tetramethyl-1,4-piperidone-N-oxyl) does not enhance production of single-strand breaks (SSB) in DNA of Chinese hamster cells irradiated under hypoxia. Misonidazole enhances the yield of SSB, but this SSB enhancement by misonidazole is reduced if TAN is present with misonidazole during irradiation. Each of these sensitizers enhances base/sugar damage, measured with the aid of bacterial enzymes (MLS, i.e., M. luteus sensitive sites). The results presented here for MLS damage in mammalian cells irradiated in the presence of the misonidazole-TAN combination indicate that the 2 drugs act independently in enhancing MLS damage, and hence they interact with different types of lesions to produce base/sugar damage. The protection by TAN in mammalian cells observed at the survival level may be due to repair of some of that type of damage which would otherwise become a misonidazole-enhanced SSB.