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

Department of Veterinary Science, 1655 Linden Drive, University of Wisconsin-Madison, Madison, Wisconsin 53706, U.S.A.

The sensitivity of the scrapie agent to u.v. 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 10^7.8 log₁₀ LD₅₀ per ml to as low as 10^4.5. Sensitivity of membrane-associated scrapie infectivity to inactivation by u.v. 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 themseleves. 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 u.v. radiation for inactivation of scrapie infectivity in the presence of chlorpromazine is an essential nucleic acid.

Keywords: scrapie, irradiation, lipid, nucleic acid, phenthiazine antipsychotics

Received 4 October 1984; accepted 19 December 1984.

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