To provide guidelines for handling the very labile
phorbol ester, RPA,2 its stability under various laboratory conditions was studied. RPA will remain undecomposed for 8 weeks if stock solutions are made in
ethanol,
ethyl acetate, or
DMSO and stored in absolute darkness at -20 degrees C. When exposed to light RPA readily isomerizes to 13'-cis-RPA. Structure/activity investigations of
irritant polyfunctional
diterpene esters of
phorbol,
ingenol, and
resiniferonol with saturated and unsaturated aliphatic or with aromatic
acids indicate that their
irritant activity is a necessary, yet insufficient prerequisite for initiation- (or
tumor-) promoting activity (e.g., Refs. 3 and 4). For further testing of this hypothesis, the
retinoic acid analogue of the mouse skin
irritant and initiation-promoter TPA, i.e., RPA, was designed (7). In initiation/promotion experiments of skin of NMRI mice, it proved to be an
irritant almost as active as TPA, but only marginally active as a promoter. In combination with TPA, it turned out to be a "second stage" promoter (PII-promoter) (1, 6) in our strain of mice (2, 7). RPA is a much more labile compound than TPA (5), especially in the solid form. If stored in
solution, special precautions have to be taken to ascertain that the concentration or dose intended is represented by undecomposed RPA.