PMID: 7546822Jan 1, 1995Paper

Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours. A review

Acta Oncologica
M R Horsman

Abstract

Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Although clinical attempts to overcome hypoxia have met with some success, the results have been far from satisfactory, and efforts are still being made to find better methods. Extensive experimental studies, especially in the last decade, have shown that nicotinamide and structurally related analogs can effectively sensitise murine tumours to both single and fractionated radiation treatments and that they do so in preference to the effects seen in mouse normal tissues. The earliest studies suggested that this enhancement of radiation damage was the result of an inhibition of the repair mechanisms, as was well documented in vitro. However, recent studies in mouse tumours have shown that the primary mode of action actually involves a reduction in tumour hypoxia. More specifically, these drugs prevent transient cessations in blood flow, thus inhibiting the...Continue Reading

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