dose-dependent InhibItion or Inhibition at all doses Retinoids, In general, exhibited strong Inhibition of ODC activity. A category of compounds showing dose-dependent Inhibition were the sulfur compounds, especIally

Ninety potential chemopreventive agents were screened using 6 theme prevendon-assodated biochemical end points. These compounds were tested using rodent (tracheal epithelial or liver) cells and human cells [neonatal foreskin fibroblasts, bronchial epithelial cells, or human leuke nile cells (HL-60)]. The effects measured were: (a) Inhibition of 12-0tetradecanoylphorbol-13-acetate (TPA)-fnduced tyrosine kinase activity in HL-60 cells; (b) Inhibition of TPA-induced ornithine decarboxylase (ODC) activity in rat tracheal epithellal cells; (c) Inhibitionof poly(ADP ribose)polymerase in propane sultone-treated primary human flbroblasts; (d) Inhibition of benzo[ajpyrene(B[a]P)-DNA binding in human bronchial epithellal cells; (e) Induction of reduced glutatbione In Buffalo rat liver cells; and (1) inhibItion ofTPA-induced free radical formation In primary human flbroblasts or HL-60 cells. Fifty compounds were highly effective In Inhibiting TPA-induced tyrosine kinase aCtivIty. This assay Identified compounds from a wide variety ofchemical classes as effective InhibItors, Including all the vitamins, retinolc acid analogues, protein kinase C In hibltors, and chemicals belongingto the amino acid category. Fifty-two chemicals were classified as highly positive compounds when examined for their abIlity to Inhibit TPA-Induced ODC activity. These agents showed a dose-dependent InhibItion or Inhibition at all doses Retinoids, In general, exhibited strong Inhibition of ODC activity. A category of compounds showing dose-dependent Inhibition were the sulfur compounds, especIally the thiols and thiones. Among the natural products, terpenes were strong inhibItors of ODC. Forty-seven compounds were classified as strong In hibltors of poly(ADP-rlbose)polymerase. In the carcInogen-DNA binding inhibItion assay, 21 compounds were identifIed as strong InhibItors, which Include phenolic compounds as well as sulfur compounds. VItamins and theIr analogues were also good Inhibitors. Testing for Induced glutathione yielded 19 compounds that were good Inducers. Sulfur-containing corn pounds and most of the phenolic compounds were also inducers of gluts thione. Twenty compounds were highly positive for InhIbItion of TPA Induced free radical formation. A significant number of phenolic and sulfur compounds were again strong oxygen radical scavengers. Some antlinflammatory agents were also Identified as free radical InhibItors. In general, retinolds were quite active In all the assays. Eight compounds were positive In all of the six assays; these were vItamin C (ascorbic acid), blsmuththiol, esculetin, etoperldone, folk add, hydrocortisone, Indole-3carbinol, and tocopherol succinate. Agents that were positive In these assays may InhibIt the carcinogenesis process by similar mechanisms in humans and are Identified as candidates for development as chemopre ventive agents. Agents capable of InhibIting multiple mechanisms are regarded as highly promising agents for cancer chemopreventlon.