Hypoxia-specific inhibition of recovery from radiation damage by a novel 2-nitroimidazole with a theophylline side chain.
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| 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.
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| Authors | R J Hodgkiss, E Kelleher, J Parrick |
| Journal | International journal of radiation biology (Int J Radiat Biol) Vol. 61 Issue 6 Pg. 797-803 (Jun 1992) ISSN: 0955-3002 [Print] England |
| PMID | 1351530 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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