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Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN

1
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA
2
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
Cancers 2014, 6(2), 1138-1156; https://doi.org/10.3390/cancers6021138
Received: 6 February 2014 / Revised: 13 April 2014 / Accepted: 28 April 2014 / Published: 14 May 2014
(This article belongs to the Special Issue Tobacco-related Cancers)
Tobacco use is a major public health problem worldwide. Tobacco-related cancers cause millions of deaths annually. Although several tobacco agents play a role in the development of tumors, the potent effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are unique. Metabolically activated NNK and NNN induce deleterious mutations in oncogenes and tumor suppression genes by forming DNA adducts, which could be considered as tumor initiation. Meanwhile, the binding of NNK and NNN to the nicotinic acetylcholine receptor promotes tumor growth by enhancing and deregulating cell proliferation, survival, migration, and invasion, thereby creating a microenvironment for tumor growth. These two unique aspects of NNK and NNN synergistically induce cancers in tobacco-exposed individuals. This review will discuss various types of tobacco products and tobacco-related cancers, as well as the molecular mechanisms by which nitrosamines, such as NNK and NNN, induce cancer. View Full-Text
Keywords: tobacco; nitrosamines; cancer tobacco; nitrosamines; cancer
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MDPI and ACS Style

Xue, J.; Yang, S.; Seng, S. Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN. Cancers 2014, 6, 1138-1156.

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