MALIGNANT TRANSFORMATION OF MOUSE BALB/C3T3 CELLS INDUCED BY NANO2

The addition of sodium nitrite (NaNO2; 5-20 mM) for 72 h to mouse BALB/c3T3 cells resulted in the induction of transformed foci (type III foci) in a dose-dependent manner. The cells isolated from the NaNO2-induced transformed foci produced progressively growing tumors when inoculated into nude mice subcutaneously at an inoculum size of 1 × 106 cells per site. In contrast, the original untreated cells did not take even at an inoculum size of 1 × 106 cells per site. The possibility that NaNO2 might react with cellular or medium components to make carcinogenic N-nitrosamines and that these might induce cell transformation was examined and almost excluded. Thus, nitrite itself seems to have a cell transforming activity. Recent evidence suggests that NO2- is produced by the activated macrophage of mammals. We also detected NO2- production in culture media in the mouse macrophage-like cell Line J774-A1 after lipopolysaccharide (LPS) treatment, and also in the human promyeloleukemia cell line HL60 after differentiation into macrophage-like cells by 12-O-tetradecanoyl phorbol-13-acetate and further activation by LPS. © 1990 Oxford University Press.