Tumor Promoters, Growth Factors and Arachidonic Acid Metabolism

Abstract

Levels of prostaglandins are elevated in the blood or urines of animals carrying tumors (Levine 1981). The levels of prostaglandins in tumors, when compared to those of appropriate normal tissue, also are elevated, and arachidonic acid metabolites in the culture fluids of some, but not all, transformed cells are higher than those found in the culture fluids of non-transformed cells (Levine 1981). One of the pleiotropic biochemical responses to tumor-promoting phorbol ester treatment in mouse skin and cultured cells is increased prostaglandin synthesis (Diamond et al. 1980; Levine 1982). Tumor-promoting phorbol esters are known to be potent tumor promoters in the two-stage model of carcinogenesis. This model was originally demonstrated in skin (Berenblum 1975), but it also has been shown to be operative in liver (Armuth and Berenblum 1972; Peraino et al. 1978; Pitot and Sirica 1980), bladder (Hicks et al. 1978), mammary gland (Armuth and Berenblum 1974), stomach (Goerttier et al. 1979), and cultured cells (Mondal et al. 1976). Several inhibitors of prostaglandin synthesis are capable of inhibiting tumor promotion by a particularly potent tumor promoter,. 12-0-tetradecanoylphorbol-13-acetate (TPA), and this inhibition can be overcome by addition of a specific prostaglandin (Marks et al. 1982). These associations have challenged many investigators to demonstrate a causal relationship between prostaglandin production and tumor formation. To date, no such causal relationship has been demonstrated.