INHIBITION OF APOPTOSIS AS A MECHANISM OF TUMOR PROMOTION

Recent evidence supports the concept that tumor growth in vivo depends on evasion of normal homeostatic control mechanisms that operate thro ugh induction of cell death by apoptosis. This study tested the hypoth esis that a common property shared by known or suspected tumor promote rs is the ability to block the process of apoptosis. A total of 10 tum or promoters were tested and all. were found to inhibit DNA fragmentat ion and cell death of 7 different cell lines triggered into apoptosis by diverse agents. Resistance to apoptosis could be induced rapidly (w ithin 1 h) by treating with relatively high concentrations of promoter s. However, low physiological concentrations of promoters could also i nduce complete resistance to apoptosis after prolonged exposure (5-15 days of culture). Like tumor promotion in vivo, promoter-induced resis tance to apoptosis was reversible after culturing in the absence of pr omoter. These findings provide new insight into the mechanism of tumor promotion and suggest a novel in vitro screening assay to detect new tumor-promoting agents in the environment.