PROMOTIONAL EFFECT OF NITROSO-N-(3-KETO-1,2-BUTANEDIOL)-3'-NITROTYRAMINE (A NITROSATED MAILLARD REACTION-PRODUCT) IN MOUSE FIBROBLAST CELLS

Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (NO-NTA) is a produ ct of model browning system generated in the presence of sodium nitrit e. The chemical structure of this compound has been confirmed by UV, m ass and nuclear magnetic resonance, and infrared spectroscopy in our p revious study. A two-stage transformation protocol was used to chemica lly transform the mouse embryo fibroblasts C3H10T1/2 cells. To initiat e transformation, the cells were treated with benzo[a]pyrene (BaP) (0. 1 mg/ml), and NO-NTA (0.01, 0.1 and 1 mg/ml) was employed subsequently to complete the transformation process. Malignant transformed foci we re formed in BaP-initiated and NO-NTA promoted C3H10T1/2 cells after 8 wk. Cells treated with NO-NTA alone failed to induce transformation. However, cells initiated with BaP and promoted by cells initiated with BaP and promoted by NO-NTA demonstrated oncogenic properties. Cell li nes transformed with NO-NTA-transformed colonies exhibited enhanced gr owth rate, anchorage independence and tumorigenicity in animals relati ve to parent cells. These results indicate that NO-NTA is a new tumour promoter and may induce tumour promotion by two-stage oncogenesis. Fu rther studies on the mechanism of action of NO-NTA are now in progress . (C) 1998 Elsevier Science Ltd. All rights reserved