HUMAN PROMYELOCYTIC LEUKEMIA-CELLS (HL-60) - A NEW MODEL TO STUDY THEEFFECTS OF CHEMOPREVENTIVE AGENTS ON H2O2 PRODUCTION

Tumor promoter-stimulated polymorphonuclear leukocytes (PMNs) produce excessive H2O2, which contributes to inflammation and carcinogenesis. A new model to study 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediat ed H2O2 formation and its suppression by chemopreventive agents was de veloped using human promyelocytic leukemic HL-60 cells and validated b y comparing results with those obtained using human PMNs. Equal H2O2 ( 20 to 25 nmol/ml) was generated by TPA-activated PMNs (2.5 x 10(5)/ml) and TPA-treated dimethylsulfoxide (DMSO)-differentiated HL-60 cells ( 5 x 10(5)/ml). The chemopreventive agent-mediated inhibition of TPA-in duced H2O2 formation was also comparable in both cell types. These res ults suggest that HL-60 cells can become a useful in vitro system to s creen rapidly for chemopreventive agents and to study their properties .