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 X 10(6) cells per site. In contrast, the original untreated cells did not take even at an inoculum size of 1 X 10(7) 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 macrophages 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.
Tsuda
H
H
Life Science Research Laboratory, Japan Tobacco Inc., Kanagawa.
Hasegawa
M
M
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000378:metabolism / Q000633:toxicity*; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity; D012977:Sodium Nitrite / Q000633:toxicity*
D003470:Culture Media; D009573:Nitrites; D009602:Nitrosamines; D012977:Sodium Nitrite