NNK is a nicotinic nitrosylated derivative. It activates ERK1/2 and PKCα, and activates Bcl2 phosphorylation at Ser70, as well as c-Myc at Thr58 and Ser62.It can be used to construct mouse models of lung cancer, as well as to induce proliferation and survival of human lung cancer cells.

METHODS: CL1.0 cells were seeded in 96-well plates and treated with 0, 3 or 10 nM NNK for 24 h, followed by MTT to measure cell viability. Cells treated with 0 or 10 nM NNK for 24 h were collected and analyzed by RT-PCR. The expression of α3, α4, α5 and α7 was detected. GAPDH was used as internal control. Cells were also preincubated with -bungarotoxin (Bun, 10 nM) for 2 h and then stimulated with NNK (+, 10 nM) without (−) for 24 h. Study contactin-1 protein levels and mRNA expression.
RESULTS NNK increased contactin-1 protein levels and up-regulated contactin-1 mRNA in a dose-dependent manner, indicating that NNK may directly stimulate gene transcription and cause CL1.0 cells to exhibit weaker toxic effects. [3]

METHODS: Female A/J mice (7 weeks old) were treated with eight consecutive doses of NNK (3 μmol per week) by intragastric gavage (i.g.) or intraperitoneal injection, and the carcinogenesis of the mice was observed. RESULTS After 26 weeks, all mice developed lung adenomas. [1] METHODS: F344 rats were administered subcutaneously three times a week for 20 weeks with a total dose of 702 mg. The carcinogenesis of the mice was observed after 12 months. RESULTS 67% of the rats developed lung cancer. [2]