Evidence for the Existence of Prohapten-Activating Enzyme in the Skin: Induction of Contact Sensitivity to Monocrotaline in Mice

Summary

Many contact sensitizers do not appear to be sufficiently reactive with protein to behave as haptens. It has therefore been presumed that they are prohaptens, which become activated in or on the skin to form suitably reactive haptens. This contribution is the first to provide compelling evidence for the occurrence of this phenomenon of prohapten activation in the skin. Epicutaneous experiments were carried out in mice, using 3-methylcholanthrene (3-MC) as a known inducer of mixed function oxidase activity, piperonyl butoxide (PBO) as a known inhibitor of this activity, and monocrotaline — a pyrrolizidine alkaloid — as a presumed prohapten. The mice could be sensitized to monocrotaline after pretreatment with 3-MC, but not after pretreatment with 3-MC followed by PBO or after no pretreatment. PBO was also found to inhibit elicitation of the contact allergic reaction to monocrotaline in monocrotaline-sensitized mice. The monocrotaline is believed to have become converted into a reactive pyrrolic ester through dehydrogenation by an induced mixed function oxidase in the skin.

L. K. is grateful to the British Council for financial support. The work was made possible by a grant from the Welsh Scheme for the Development of Health and Social Research.