Promotional effect of N-nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (a nitrosated Maillard reaction product) in mouse fibroblast cells.

N-Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (NO-NTA) is a product of model browning system generated in the presence of sodium nitrite. The chemical structure of this compound has been confirmed by UV, mass and nuclear magnetic resonance, and infrared spectroscopy in our previous study. A two-stage transformation protocol was used to chemically transform the mouse embryo fibroblasts C3H10T1/2 cells. To initiate 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 were 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 lines transformed with NO-NTA-transformed colonies exhibited enhanced growth rate, anchorage independence and tumorigenicity in animals relative to parent cells. These results indicate that NO-NTA is a new tumour promoter and may induce tumour promotion by two-stage oncogenesis. Further studies on the mechanism of action of NO-NTA are now in progress.