ABROGATION OF THE SUPPRESSIVE EFFECT OF 12-O-TETRADECANOYLPHORBOL 13-ACETATE AND 7,12-DIMETHYLBENZ[A]ANTHRACENE ON FOOTPAD REACTION OF MICE BY INDOMETHACIN AND SOME INHIBITORS OF TUMOR PROMOTION

Influences of indomethacin, which has been known as an inhibitor of the production of prostaglandins, on the suppression of footpad reaction (FPR) of BALB/c mice against sheep red blood cells by the painting of 12-O-tetradecanoylphorbol 13-acetate (TPA, a typical tumor promoter) were studied. The temporary suppressive effect by the painting of TPA (8 nmol) was abrogated by the painting of indomethacin (7-70 nmol) 60 min before TPA treatments. The lasting suppressive effect by TPA treatment (8 nmol/d) for 7 d following the painting of 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol), which is a typical tumor initiator, also disappeared when indomethacin (7 nmol) was painted 30-90 min before each TPA treatment. Influences of some inhibitors of tumor promotion on the lasting suppressive effect of FPR by DMBA and TPA were also tested. Painting of 0.6-mu-mol of 1-phenyl-2-pyrazolidone, 8.2 nmol of salcophytol A, 17 nmol of retinoic acid, 5.6-mu-mol of 3(2)-tert-butyl-4-hydroxyanisol, and 3-mu-mol of quercetin 45 min before each TPA treatment decreased the suppressive effect on the footpad reaction.