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 initiator and promoter on mouse C3H10T1/2 cells. In this study, a two-stage skin carcinogenesis protocol was used to promote CD-1 mouse skin carcinogenesis 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 in mice treated with BaP or treated with NO-NTA alone. The NO-NTA-promoted tumors that were observed histologically in mice showed well-differentiated squamous cell carcinoma with invasion into the subcutaneous region. Application of the same amount of NO-NTA not only caused significant induction of hyperplasia but also epidermal ornithine decarboxylase (ODC) activity. Treatment of mouse skin (1 cm(2)) with various amounts of NO-NTA (10, 50, or 250 nmol) caused production of hydrogen peroxide by 1.63-, 1.91-, and 2. 38-fold, respectively, and marked induction of myeloperoxidase (MPO) by 21-, 39-, and 61-fold. These results indicate that NO-NTA is a new tumor promoter and may induce tumor promotion by oxidant stress in CD-1 mouse skin.
Chang
W C
WC
Department of Medical Technology, Chung Hwa College of Medical Technology, Tainan, Taiwan.
Chen
C C
CC
Tseng
T H
TH
Huang
H P
HP
Hsu
J D
JD
Wang
C J
CJ
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced; D004789:Enzyme Activation; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced; D015416:Maillard Reaction; D051379:Mice; D015538:Nitrosation; D009955:Ornithine Decarboxylase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced*; D014439:Tyramine / Q000031:analogs & derivatives* / Q000633:toxicity*
D002273:Carcinogens; C098876:N-nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D009955:Ornithine Decarboxylase; D014439:Tyramine