Smoking is the number one cause of preventable death in the United States. Approximately one in every five deaths is due to complications related to smoking. The harmful effects of smoking are due to several factors including the smoke from tobacco and nicotine. Nicotine is an extremely potent and toxic chemical. Its effects can be experienced almost immediately.

Green Tobacco Sickness
Green tobacco sickness is experienced when skin comes into contact with green tobacco leaves for a long period of time. Green tobacco sickness is similar to directly ingesting a larger dose of nicotine in that the symptoms include nausea and vomiting. Other symptoms include headaches, happiness, loss of appetite, tiredness, and fast and abnormal heartbeat (tachyarrhythmia).

Nicotine and Cancer
Nicotine promotes several types of cancers primarily by promoting progression of cancer cells. However, nicotine can also activate pathways in noncancerous cells that promote transformation. Activation of nACHRs by nicotine activates signaling pathways that promote survival of unhealthy cells. Nicotine is also converted into carcinogenic tobacco specific nitrosamines (TSNAs), specificallynitrosonornicotineine (NNN), and Nicotine-derived nitrosamine ketone (NNK), through a process called nitrosation in the mouth. Nicotine also activates factors such as nuclear factor kappa B (NF-kB) that enhance cancer cell division and survival. In addition to promoting cancer cell survival, nicotine prevents cancer cell death mechanisms.

Nicotine can also promote cancer in normal cells by generating DNA mutations. It is transformed into metabolites that promote cell proliferation. Nicotine stimulates cell transformation into cancer cells by enhancing cell proliferation and improving survival. The cancer promoting effects of nicotine work with other carcinogens in the environment to promote rapid cancer development.

Lung Cancer
Smoking is the cause of 90% of lung cancer deaths. There is some evidence that the rate of metabolism of nicotine may influence a smoker’s risk for developing lung cancer. Nitrosamine NNK contributes to lung cancer development. NNK’s carcinogenic properties are activated in part by nicotine metabolizer CYP2A6. Thus, individuals that metabolize nicotine more slowly smoke fewer cigarettes and ingest lower levels of NNK. Which means there is less NNK that can be transformed into carcinogens. Although there is some evidence that this is the case, particularly in Asian communities when compared to Caucasian communities. There are other studies that do not support this theory.

Hyperoxia which is exposure to excess oxygen in combination with a genetic predisposition can induce lung cancer. Cotinine, the metabolite resulting from the breakdown of nicotine has also been shown to promote lung tumor formation by blocking the activity of anti-apoptosis pathways. Nicotine itself promotes lung cancer progression and even metastasis by supporting mechanisms that sustain tumor growth and survival, such as angiogenesis.

Gastrointestinal Cancer
Nicotine promotes the survival of cancer cells by binding to cell surface receptors. These receptors activate downstream pathways that increase cell resistance to chemotherapies. Not surprisingly, patients with cancer that are receiving chemotherapy have a worse prognosis when they continue to smoke during treatment due to increased toxicity and lower efficacy of the chemotherapies.

Other Cancers
There is also evidence of nicotine promotes pancreatic and breast cancers by activating pathways that facilitates tumor growth, metastasis, and chemoresistance.