EFFECTS OF ANTIINFLAMMATORY AGENTS ON MOUSE SKIN TUMOR PROMOTION, EPIDERMAL DNA-SYNTHESIS, PHORBOL ESTER-INDUCED CELLULAR PROLIFERATION, AND PRODUCTION OF PLASMINOGEN ACTIVATOR
The antiinflammatory steroids fluocinolone acetonide, fluocinonide and fluclorolone acetonide were effective inhibitory agents of mouse skin tumor promotion. These steroids also drastically inhibited epidermal DNA synthesis and epidermal cellular proliferation induced by a phorbal ester tumor promoter. These compounds were also potent inhibitors of plasminogen activator production in tumor cell cultures. The clinically used nonsteroidal antiinflammatory agents oxyphenbutazone, indomethacin and Seclazone also inhibited tumor promotion but were less effective. Although these agents are useful against inflammatory disorders in general when given p.o. [orally], in these studies they had little effect on inflammation and epidermal cellular proliferation induced by a phorbol ester tumor promoter when given topically. The aforementioned nonsteroidal antiinflammatory agents also had little effect on epidermal DNA synthesis. Oxyphenbutazone and indomethacin were less potent inhibitors of plasminogen activator production in tumor cells than the antiinflammatory steroids, and Seclazone produced a negligible inhibition. There is a general correlation in the potencies of a series of steroidal antiinflammatory agents for inhibition of tumor promotion and their ability to inhibit plasminogen activator production by tumor cell cultures and epidermal DNA synthesis.