Inactivation of the Scrapie Agent by Ultraviolet Irradiation in the Presence of Chlorpromazine

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Abstract
The sensitivity of the scrapie agent to UV inactivation was found to be related to the purity of the tissue preparation. Scrapie infectivity associated with membrane vesicles was unaffected when irradiated with 104 J/m2. Irradiation of more highly purified preparations from detergent-extracted CsCl gradient fractions reduced scrapie infectivity from 107.8 log10 LD50/ml to as low as 104.5. Sensitivity of membrane-associated scrapie infectivity to inactivation by UV irradiation could be increased by addition of chlorpromazine, a phenthiazine antipsychotic which penetrates lipid bilayers and induces single-strand breaks in nucleic acids under irradiation. Chlorpromazine without irradiation, and a semiquinone protein-binding radical of chlorpromazine, failed to decrease scrapie infectivity by themselves. A closely related phenthiazine antipsychotic, trifluoperazine, which does not bind to nucleic acids, did not reduce scrapie infectivity. These findings suggest that the target of UV radiation for inactivation of scrapie infectivity in the presence of chlorpromazine is an essential nucleic acid.