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Diphenylcyclopropenone (DPCP) has recently been reported to be a potent contact sensitizer for the treatment of alopecia areata. DPCP is nonmutagenic in the Ames assay. Studies on chemical purity, stability, and mechanisms of action are lacking. DPCP is synthesized by cyclization of alpha, alpha'-dibromodibenzylketone. The latter elicits a reaction in guinea pigs sensitized to DPCP. We examined a commercial sample of DPCP by gas chromatography--mass spectrometry for the presence of contaminants. The stability of dilute solutions of DPCP in ethanol and cyclohexane to fluorescent light, sunlight, and heat was followed by ultraviolet (UV) spectrometry. The isosbestic point and half-life for this reaction were determined. We found no original or intermediate reagents in our sample. DPCP was found to decompose, forming diphenylacetylene on exposure to both sunlight and fluorescent light in less than 2 weeks. Samples shielded from the light at -70 degrees C and at room temperature were stable over a 4-week period. The extent of decomposition was the same in both ethanol and cyclohexane. It is possible that DPCP may act as a prosensitizer with the actual sensitizer liberated by a photoactivated intermediate (stable, metastable, or unstable) or a combination of these.

The photochemical conversion of diphenylcyclopropenone to diphenylacetylene has recently been reported. Diphenylcyclopropenone is used in the treatment of alopecia areata and is nonmutagenic in a limited Ames assay. We examined diphenylcyclopropenone and diphenylacetylene, as well as synthetic precursors of diphenylcyclopropenone--dibenzylketone and alpha,alpha'-dibromodibenzylketone--for mutagenicity against TA100, TA98, TA102, UTH8413, and UTH8414. All compounds were nonmutagenic except alpha,alpha'-dibromodibenzylketone, which was a potent mutagen in TA100 with and without S-9 activation. The effect of photochemical activation of diphenylcyclopropenone in the presence of bacteria demonstrated mutagenicity in UTH8413 (two times background) at 10 micrograms/plate with S-9 microsomal activation. 8-Methoxypsoralen produces a mutagenic response in TA102 at 0.1 microgram/plate with 60 seconds of exposure to 350 nm light. In vitro photochemically activated Ames assay with S-9 microsomal fraction may enhance the trapping of short-lived photochemically produced high-energy mutagenic intermediates. This technique offers exciting opportunities to trap high-energy intermediates that may play an important role in mutagenesis. This method can be applied to a variety of topically applied dermatologic agents, potentially subjected to photochemical changes in normal use.