Biomedical subjects
Publications and source records attributed to J L Redpath.
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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Cetylpyridinium chloride has been shown to be an effective radiosensitizer of both oxic and anoxic suspensions of Serratia marcescens in buffer. The related compounds ethylpyridinium bromide and cetyltrimethylammonium chloride exhibited no such radiosensitizing properties at comparable concentrations. It is suggested that the efficiency of cetylpyridinium chloride is due to the combination of lipid-soluble (cetyl) and electron-affinic (pyridinium) moieties within the same molecule, and that these may provide for interaction with a membrane-associated target. Cetylpyridinium chloride did not radiosensitize bacteria suspended in nutrient broth.
Evidence for the involvement of O-2 ions in the formation of N'-Formylkynurenine, a major tryptophan oxidation product is presented on the basis of radiolysis and electrochemistry data. The biological importance of such a reaction is discussed.
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The influence of persulphate ions on the radiosensitivity of dilute aqueous solutions of ribonuclease and lysozyme has been studied under a variety of conditions. Rate-constants for reactions of the sulphate radical, SO4, with a variety of solutes and transient product spectra of some of these reactions are reported. The presence of persulphate ions in general enhances the radiation sensitivity; in nitrous-oxide-saturated persulphate solution, a chain reaction has been demonstrated.
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The radiation-induced inactivation of dilute solutions of three forms of bovine carbonic anhydrase (metal-free apo-BCA, Zn2+-BCA and Co2+-BCA) has been studied. The presence of the metal ions did not alter the sensitivity of the enzyme to inactivation by oxidizing radicals; however, they exerted a protective effect against inactivation by reducing radicals. Data obtained using the amino-acid-specific inorganic radical anions (CNS)2-and Br2-allowed the identification of histidine, tyrosine and tryptophan as residues essential to the activity of bovine carbonic anhydrase when assayed by p-nitro-phenylacetate.
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Radiolysis of N2O-saturated solutions of transfer RNA (tRNA) and the arylacethydroxamic acids, N-hydroxy-N-2-acetylaminofluorene and N-hydroxy-N-4-acetylaminobiphenyl; their corresponding acetamides, 2-acetylaminofluorene and 4-acetylaminofluorene; or the O-glucuronide of N-hydroxy-N-2-acetylaminofluorene resulted in adduct formation of the nucleic acid with these carcinogenic arylamine derivatives. The yield of adducts on irradiation of the arylacethdroxamic acids with tRNA was greater than that for their corresponding acetamides or the O-glucuronide. The fluorenylacethydroxamic acid and acetamide were also more reactive than the biphenyl analogs. Adduct formation resulting from radiolysis of tRNA and the arylacethydroxamic acids or the O-glucuronide proceeded with retention of both the aromatic nucleus and the N-acetyl group. The yields of adducts were much greater for irradiated mixtures than for irradiation of either component alone followed by mixing. Evaluation of the data shows that initial modification of the tRNA or the carcinogen can lead to adduct formation. In the case of primary radical attack of the nucleic acid, it has been shown that short-lived reactive RNA intermediates are responsible for a major fraction of the observed yield of adducts in the irradiated mixtures. Comparative studies showed that irradiation under conditions that favor reaction of oxidizing radicals enhanced formation of the adducts. Oxygen was shown to protect RNA from irradiation-induced binding of the arylacethydroxamine acids due to competition of O2 with the carcinogen for the reactive RNA intermediates.
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