Hypoxia-specific inhibition of recovery from radiation damage by a novel 2-nitroimidazole with a theophylline side chain.

Abstract:

:A novel 2-nitroimidazole with a theophylline side-chain, 7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline, (NITP) was as efficient a hypoxic-cell radiosensitizer as misonidazole. However, if cells were irradiated with NITP under hypoxic conditions and then exposed to the drug under aerobic conditions, a much larger radiosensitizing effect was observed, partly because of a reduction in the size of the shoulder of the survival curve. There was little effect of NITP on the radiosensitivity of well oxygenated cells, even with post-irradiation drug contact. Split-dose survival curves showed that the drug inhibited recovery from radiation damage only when the cells were irradiated under hypoxia but not when irradiations were under oxic conditions. A reduction in the size of the shoulder of the survival curve should allow the hypoxic-cell radiosensitizing efficiency of NITP to be maintained with low doses of radiation used in multifraction cancer radiotherapy. Bifunctional drugs containing both electron-affinic and repair inhibiting groups may represent a new approach to the synthesis of hypoxic-cell targeted adjuncts to radiotherapy.

journal_name

Int J Radiat Biol

authors

Hodgkiss RJ,Kelleher E,Parrick J

doi

10.1080/09553009214551671

subject

Has Abstract

pub_date

1992-06-01 00:00:00

pages

797-803

issue

6

eissn

0955-3002

issn

1362-3095

pii

2LRM3HCCPEGHAB1A

journal_volume

61

pub_type

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