Proceedings: Metabolites of benzo (A) pyrene (BP) which bind to DNA.
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Biomedical subjects
Publications and source records attributed to M H Thompson.
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Rat liver microsomes (induced by 3-methylcholanthrene) were used to catalyze the binding of tritium-labeled benzo(alpha)pyrene to DNA. Enzymic degradation of this DNA to deoxyribonucleosides, followed by separation of the products by Sephadex LH20 column chromatography, revealed two major products. One of these was shown to be the same as that obtained from DNA with benzo(alpha)pyrene bound following treatment of mouse embryo cells in culture with the carcinogen. Neither product resembled those obtained from DNA that had been caused to react with benzo(alpha)pyrene 4,5-oxide (K-region eposide). The aryl hydrocarbon hydroxylase activity of the microsome preparations was determined and related to the extent of microsome-catalyzed hydrocarbon binding. Inhibitors of the enzyme epoxide hydrase increased this binding but caused the loss of one of the two major products. On the basis of the results obtained, a model is proposed of the mechanism of benzo(alpha)pyrene metabolism and DNA binding.
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Putative transmitters and related substances were perfused through the guinea pig scala tympani while monitoring the compound action potential of the cochlear nerve (AP) and the cochlear microphonic potential. Various substances were then ranked according to their ability to reduce the AP. The more active compounds ranked: methysergide (1 mM) greater than ATP (10 mM) = tyramine (10 mM) greater than salicylate (10 mM) greater than bicuculline (10 mM) greater than asparate (10 mM) greater than glutamate (10 mM) greater than citrate (10 mM) greater than dextrose (100 mM) greater than glycine (100 mM) greater than GABA (100 mM) greater than prostaglandin E2 (1 mM) greater than serotonin (10 mM). The activity of substances at 100 mM indicates a physical, osmotic change in the cochlear structure. Activity at 10 mM and 1 mM indicated afferent transmitter-like activity for the putative transmitters and interference with the endogenous transmitter for related substances. It is concluded that several substances can be eliminated as afferent transmitter candidates, while others warrant further examination.