Tumor promotion of N-nitroso-N-(3-keto-1,2-butanediol)-3 '-nitrotyramine derived from nitrosation of Maillard reaction product in CD-1 mice

N-Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (NO-NTA) is a product of a model browning system generated in the presence of sodium nitrite, Our previous study showed that NO-NTA had genotoxicity and proved to be an ini tiator and promoter on mouse C3H10T1/2 cells. In this study, a two-stage sk in carcinogenesis protocol was used to promote CD-I mouse skin carcinogenes is using NO-NTA. Twice weekly, for 38 weeks, topical application of NO-NTA at the concentration of 250 nmol to mice previously initiated with benzo(a) pyrene (BaP) caused 90% tumor incidence. However, no tumors were observed i n mice treated with BaP or treated with NO-NTA alone. The NO-NTA-promoted t umors that were observed histologically in mice showed well-differentiated squamous cell carcinoma with invasion into the subscutaneous region. Applic ation of the same amount of NO-NTA not only caused significant induction of hyperplasia but also epidermal ornithine decarboxylase (ODC) activity Trea tment of mouse skin (1 cm(2)) with various amounts of NO-NTA (10, 50, or 25 0 nmol) caused production of hydrogen peroxide by 1.63-, 1.91-, and 2.38-fo ld, respectively, and marked induction of myeloperoxidase (MPO) by 21-, 39- , and 61-fold. These results indicate that NO-NTA is a new tumor promoter a nd may induce tumor promotion by oxidant stress in CD-1 mouse skin, (C) 200 0 Academic Press.