Aposcreen--A Novel Test for Tumor Promoters

Currently there are a variety of in vitro screening assays used to test environmental compoundsand potential drugs for mutagenic and carcinogenic activity. However, these assays generally do notdetect tumor promoters, thus economical screens for these agents are urgently needed. This applicationwill develop and test a novel, inexpensive in vitro screening assay to test large numbers of environmentalcompounds and drugs for tumor promoting activity. This assay is based on the new finding that manyor all tumor promoters can inhibit or induce cellular resistance to the physiological process of cell deaththrough apoptosis. The assay, termed, ApoScreen, will be validated by testing a panel of knownpromoters and non-promoting agents to determine if their effects on apoptosis correlate with previouslypublished results in animal models of tumor promotion. The human U937 tumor cell line will be treatedwith each test agent using a high dose acute exposure or a low physiological dose chronic exposureprotocol. Apoptosis in response to tumor necrosis factor or UV light will be assessed by measuring DNAfragmentation in an assay requiring only 2-3 hr. incubation. If ApoScreen shows good predictive ability,it will ultimately be used in conjunction with other surrogate assays to screen large numbers ofcompounds for those exhibiting tumor promoter characteristics. The most suspicious compounds canthen be tested in the more expensive and time consuming animal models of tumor promotion. Thisapproach should provide an efficient and economical mechanism to identify potentially dangerouscompounds and reduce human exposure to tumor promoting agents.