Further studies on Cerenkov-induced photoreactivatable damage in E. coli.
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Biomedical subjects
Publications and source records attributed to J L Redpath.
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The interaction of Adriamycin with radiation damage in the mouse lung has been shown to disappear with the same kinetics as those for the 'slow repair' of such radiation damage. Split-dose experiments have demonstrated that Adriamycin inhibits this 'slow-repair' process whereas the drug has no effect on the repair of sublethal damage in irradiated mouse lung.
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The effect of Adriamycin (doxorubicin hydrochloride) (10 mg/kg intraperitoneally) on the response of mouse gut to irradiation with 6-MVp photons or fast neutrons (67 MeV p--Be), was assessed with the six-day death endpoint. The drug reduced the LD50/6 by the same factor (approximately 1.25) for both types of radiation. Thus, the radiobiological effectiveness (RBE) (photons/neutrons) for gut damage is unaltered by the addition of Adriamycin. The data indicated no significant effect of drug scheduling if given within 16 hours before or after irradiation.
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Both eaq- and .OH have been found to react with 8-methoxypsoralen (8-MOP), giving rate-constants of 1.1 X 10(10) M-1 s-1. Transient spectra of products from the reactions of eaq-, .OH with 8-MOP have been characterized. Rate-constants for the oxidation by 8-MOP of reduced and oxidized DNA bases have also been measured and found to lie in the range 3-6 X 10(9) M-1 s-1. Oxidation of reduced bases occurs by electron transfer with 100 per cent efficiency in all cases. However, for oxidized bases, only approximately 25 per cent of the intermediate yield produced by OH attack undergoes electron transfer; the balance of the oxidized base appears to form adducts with 8-MOP.
The radiosensitivity of E. coli AB2463 recA, given as the reciprocal of the mean lethal dose, Do-1, has been shown to be the same for four fast neutron beams with widely different energy spectra. It is proposed that this organism can be used to intercompare dosimetry on fast neutron beams with mean energies in the range 4 to 25 MeV with an accuracy of +/- 5%.
8-Methoxypsoralen has been shown to act as a radiosensitizer of hypoxic bacteriophage and bacteria. Radiosensitization of bacteriophage requires irradiation in the presence of excess scavenger. Bacterial radiosensitization requires deficiencies in uvr and rec genes. For the drug to be effective it must be present during irradiation. Pulse radiolysis studies have shown that, like electron-affinic radiosensitizers, 8MOP can efficiently oxidize free radicals. Unlike oxygen and most electron-affinic radiosensitizers 8MOP does not act in a purely dose-modifying fashion, and can radiosensitize beyond the oxygen effect.
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8-Methoxypsoralen has been shown to act as a radiosensitizer of hypoxic bacterial cells with uvrA, recA and uvrB and/or lexA mutations. No effect of the drug on the radiosensitivity of oxic bacteria with these mutations was observed. This drug differs from O2 and electron-affinic radiosensitizers in that its effect is not purely dose-modifying and can exceed the oxygen effect in certain mutants.
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