TUMOR-PROMOTING ACTIVITY OF 2,3-DIHYDROPHORBOL MYRISTATE ACETATE AND PHORBOLOL MYRISTATE ACETATE IN MOUSE SKIN

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (4) , 921-925
Abstract
Phorbolol myristate acetate (PHMA) was previously prepared from the potent mouse skin tumor promoter phorbol myristate acetate (PMA) by sodium borohydride reduction of the C-5 carbonyl group in PMA to a secondary alcohol. PHMA had an inflammatory effect in mouse skin equal to that of PMA. 2,3-Dihydrophorbol myristate acetate (DPMA), a new compound, was prepared from the 3-aldehyde of PMA by catalytic hydrogenation. DPMA exhibited no detectable inflammatory effect in mouse skin. DPMA and PHMA were tested on the dorsal skins of female ICR/Ha Swiss mice (30/group) for 433 and 380 days, respectively, in separate experiments. The tumor-promoting activity of both compounds was reduced significantly, compared with that of equimolar doses of PMA. For each treatment the number of mice with tumors per total number of tumors was: DPMA, 9/17, PMA, 29/553 at 10 .mu.g/mouse; PMA, 30/317; PHMA, 24/69 at 2.5 .mu.g/mouse. The results suggest that specific binding requirements influence the tumor-promoting and hyperplastic activity of PMA and its closely related derivatives in mouse skin.