Toxico-Epigenomic Mechanisms of Smoking Exposure in Lung Cancer Development
Main Article Content
Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with cigarette smoking recognized as the primary environmental risk factor contributing to its development. Tobacco smoke contains various carcinogenic compounds that induce oxidative stress and epigenetic alterations, including DNA methylation and histone modifications, which regulate gene expression without altering the DNA sequence. This review aimed to examine the toxico-epigenomic mechanisms underlying smoking-induced lung carcinogenesis, particularly the roles of nicotine-derived nitrosamine ketone (NNK), carbon monoxide, DNA methyltransferases (DNMTs), and chromatin modifications. This study employed a narrative literature review approach by analyzing relevant peer-reviewed scientific publications focusing on tobacco toxicology, epigenetic regulation, and lung cancer mechanisms. The findings indicated that NNK contributes to lung carcinogenesis through DNMT1 stabilization, promoter hypermethylation, and the silencing of tumor suppressor genes, while carbon monoxide promotes hypoxia and reactive oxygen species generation, further enhancing epigenetic dysregulation. These mechanisms influence critical biological processes, including cell proliferation, apoptosis, DNA repair, and tumor progression. Understanding smoking-related epigenetic alterations provides important insights for developing early diagnostic biomarkers and targeted therapeutic strategies, including DNMT inhibitors such as 5-azacitidine, 5-aza-2'-deoxycytidine, and zebularine. This review highlights the importance of integrating toxico-epigenomic approaches to improve understanding and management of smoking-related lung cancer.
Keywords:
toxico-epigenomics, DNA methylation, lung cancer
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Costelloa, Joseph F., and Plass, Christoph . (2001). Methylation matters . Journal of Medical Genetic. 38 (5), p285-303.Aniruddha, Chatterjee. Euan, J Rodgera.Eccles, Michael R. (2018). Epigenetic drivers of tumourigenesis and cancer metastasis. Seminars in cancer biology. 51 (1), p149-159.
Debina Sarkar, Euphemia Y Leung, Bruce C Baguley, Graeme J Finlay & Marjan E Askarian-Amiri. (2015). Epigenetic regulation in human melanoma: past and future. Epigenetics. 10 (2), p 103-121.
Diane E. Handy, PhD, Rita Castro, PhD, and Joseph Loscalzo, MD, PhD. (2011). Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular Disease. Circulation. 123 (19), p2145-2156.
Flotho, C. Claus, R. Batz, C. Schneider, M. Sandrock, I. Ihde, S. Plass, C. Niemeyer, C. M. & Lübbert, M . (2009). The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. 23 (1), p1019–1028.
Ghavifekr Fakhr, M., Farshdousti Hagh, M., Shanehbandi, D., & Baradaran, B. (2013). DNA methylation pattern as important epigenetic criterion in cancer. Genetics research international, 2013(1), p317569.
Handy, PhD,Diane E.Castro, PhD,Rita.and Loscalzo, MD, PhD,Joseph. . (2012). Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular Disease. Circulation. 123 (19), p2145–2156.
Hecht S. S. (2014). It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco. Cancer prevention research (Philadelphia, Pa.), 7(7), p639-47.
Hirota T. (2018). Epigenetic Regulation of Pharmacokinetic-related Genes in Human Tissues. Yakugaku Zasshi. 138 (11), p1391-1396.
Huyn, Nam Cong-Nhat.Everts, Vincent.Ampornaramveth, Ruchanee Salingcarnboriboon.. (2017). Histone deacetylases and their roles in mineralized tissue regeneration. Bone Reports. 7 (1), p33-40.
Irvine, Ryan A. Lin,Iping G. and Hsieh, Chih-Lin. (2002). DNA Methylation Has a Local Effect on Transcription and Histone Acetylation. Molecular and Cellular Biology. 22 (19), p6689–6696.
Jin, Lihua. Hanigan, Christin L. Wu, Yu. Wang, Wei. Park, Ben Ho. Woster, Patrick M. and Robert A. Casero, Jr. (2013). Loss of LSD1 (lysine-specific demethylase 1) suppresses growth and alters gene expression of human colon cancer cells in a p53- and DNMT1(DNA methyltransferase 1)-independent manner. Biochemical Journal. 449 (2), p459-468.
Jin, Zhaohui. Gao, Fengqin. Flagg, Tammy. and Deng, Xingming. (2004). Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation.. The Journal of Biological Chemistry. 279 (38), p40209-40219.
Jones, P. A., & Liang, G. (2009). Rethinking how DNA methylation patterns are maintained. Nature reviews. Genetics 10(11). p805-11.
Jyoti Malhotra, Matteo Malvezzi, Eva Negri, Carlo La Vecchia, Paolo Boffetta. (2016). Risk factors for lung cancer worldwide. European Respiratory Journal. 52 (5), p40.
Kazanets, Anna. Shorstova, Tatiana. Hilmi, Khalid.Marques, Maud. Witcher, Michael. (2016). Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1865 (2), p275-288.
Kim, J. A., & Yeom, Y. I. (2017). Metabolic Signaling to Epigenetic Alterations in Cancer. Biomolecules & therapeutics, 26(1), p69-80.
Lawrence, Moyra.Daujat, Sylvain.Schneider,Robert . (2016). Lateral Thinking: How Histone Modifications Regulate Gene Expression. Trend in Genetic. 32 (1), p42-56.
Lin., Ruo-Kai. Hsieh., Yi-Shuan. Lin., Pinpin. Hsu., Han-Shui. Chen.,Chih-Yi. Tang.,Yen-An. Lee., Chung-Fan. and Wang., Yi-Ching. (2010). The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor suppressor gene hypermethylation in mice and lung cancer patients. J Clin Invest. 120 (2), p521–532.
Lopez-Serra, L. Esteller, M. (2008). Proteins that bind methylated DNA and human cancer: reading the wrong words. British Journal of Cancer. 98 (12), p1881-1885.
McKeown S. R. (2014). Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. The British journal of radiology, 87(1035), p20130676.
Meng,Min. Zhao, Xin-Han. Ning, Qian. Hou, Lei. Xin, Guo-Hong. and Liu, Li-Feng . (2012). Tumor stem cells: A new approach for tumor therapy . Oncology Letters. 4 (2), p187-193.
Moore, L. D., Le, T., & Fan, G. (2012). DNA methylation and its basic function. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 38(1), p23-38.
Muz, B., de la Puente, P., Azab, F., & Azab, A. K. (2015). The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckland, N.Z.), 3(1), p83-92.
Nan, Xinsheng Ng, Huck-Hui Johnson, Colin A. Laherty, Carol D. Turner, Bryan M. Eisenman, Robert N. and Bird, Adrian. (1998). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 393 (1), p386-389.
Nivedita, Chatterjee. Jiwan, Gim. and Jinhee, Choi. (2018). Epigenetic profiling to environmental stressors in model and non-model organisms: Ecotoxicology perspective. Environemental health and toxicology. 33 (3), p e2018015.
Nyström, Minna. and Mutanen, Marja. (2009). Diet and epigenetics in colon cancer. World Journal of Gastroenterology. 15 (3), p257-263.
Ovesen, Jerald. Puga, Alvaro.Schnekenburger, Michael. (2011). Aryl Hydrocarbon Receptor Ligands of Widely Different Toxic Equivalency Factors Induce Similar HistoneMarksin Target Gene Chromatin. Toxicological Sciences. 121 (1), p123-131.
Parascandola, M. (2004). Skepticism, statistical methods, and the cigarette: a historical analysis of a methodological debate. Perspective in Biology and Medicine. 47 (2), p244-261.
Peter W. Laird. (2003). Review Article | Published: 01 April 2003 Early detection The the promise of DNA methylation markers. Nature Reviews Cancer. 3 (1), p253–266.
Peterson, Lisa A. (2017). Context Matters: Contribution of Specific DNA Adducts to the Genotoxic Properties of the Tobacco-Specific Nitrosamine NNK. Chemical Research in Toxicology. 30 (1), p 420–433.
Philibert, R. A., Beach, S. R., & Brody, G. H. (2014). The DNA methylation signature of smoking: an archetype for the identification of biomarkers for behavioral illness. Nebraska Symposium on Motivation. Nebraska Symposium on Motivation, 61, 109-27.
Ransohoff, J. D., Wei, Y., & Khavari, P. A. (2017). The functions and unique features of long intergenic non-coding RNA. Nature reviews. Molecular cell biology, 19(3), 143-157.
Reamon-Buettner, SM. Mutschler, V. Borlak, J. (2008). The next innovation cycle in toxicogenomics: environmental epigenetics. Mutation research. 659 (1-2), p158-165.
Sánchez-Pernaute, Olga. (2017). Epigenetic therapies, still in the midway between facts and fiction. Reumatologia Clinica. 13 (6), p311-370.
Schiffmann, Insa. Greve, Gabriele. Jung, Manfred. and Lübberta, Michael . (2016). Epigenetic therapy approaches in non-small cell lung cancer: Update and perspectives. Epigenetics. 11 (12), p858–870.
Schulz, W.A. Steinhoff, C. Florl, AR. (2006). Methylation of endogenous human retroelements in health and disease. currents topic in microbiology and immunology. 310 (1), p211-250.
Scott M. Langevin, Robert A. Kratzke, and Karl T. Kelsey. (2016). Epigenetics of Lung Cancer. Transl Res. 165 (1), p74-90.
Seaberg, R. M.; Van Der Kooy, D. (2003). "Stem and progenitor cells: The premature desertion of rigorous definitions". Trends in Neuroscience. 26 (3), p125-131.
Severin, P. M., Zou, X., Gaub, H. E., & Schulten, K. (2011). Cytosine methylation alters DNA mechanical properties. Nucleic acids research, 39(20), p8740-51.
Shi L, Zheng M, Hou J, Zhu B, Wang X. (2016). Regulatory roles of epigenetic modulators, modifiers and mediators in lung cancer. Seminars in cancer biology. 42 (3), p4-12.
Shih, Yin-Hwa. Shieh, Tzong-Ming. (2017). Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers. International Journal of Molecular Science. 18 (6), p1210.
Shikhar Sharma, Theresa K. Kelly, Peter A. Jones. (2010). Epigenetics in cancer. carcinogenesis. 31 (1), p27–36.
Singh, Sandeep. Chellappana, Srikumar. (2014). Lung cancer stem cells: Molecular features and therapeutic targets. Molecular Aspects of Medicine. 39 (1), p50-60.
Steinberg S. F. (2012). Regulation of protein kinase D1 activity. Molecular pharmacology, 81(3), p284-291.
Struhl K. (2014). Is DNA methylation of tumour suppressor genes epigenetic?. eLife. 3(1). p e02475.
Suarez-Ulloa V, Gonzalez-Romero R, Eirin-Lopez J.M. (2015). Environmental epigenetics: A promising venue for developing next-generation pollution biomonitoring tools in marine invertebrates. Marine Pollution Bulletin. 98 (1-2), p5-13.
Subramaniam, Dharmalingam. Thombre, Ravi. Dhar, Animesh. and Anant, Shrikant. (2014). DNA Methyltransferases: A Novel Target for Prevention and Therapy. Front Oncol. 4 (80), [doi: 10.3389/fonc.2014.00080].
Svedruži?, Željko M.and Reich, Norbert O. (2005). DNA Cytosine C5 Methyltransferase Dnmt1:? Catalysis-Dependent Release of Allosteric Inhibition. Biochemistry. 44 (27), p9472–9485.
Tarang, S., Kumar, S., & Batra, S. K. (2012). Mucins and toll-like receptors: kith and kin in infection and cancer. Cancer letters, 321(2), p110-9.
Tong-Hong Wang, Shih-Min Hsia, Yin-Hwa Shih, and Tzong-Ming Shieh 8. (2017). Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers. International Journal of Molecular Science. 18 (6), doi:10.3390/ijms18061210.
Verma M. (2015). Toxicoepigenomics and cancer: implications for screening. Methods in Molecular Biology. 1238 (1), p355-367.
Wang, Yan.Sun, ZhongSheng. and Szyf, Moshe. (2017). S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells. Oncotarget. 8 (67), p111866–111881.
Wardlaw, S.A. Nikula,K.J. Kracko, D.A. Finch,G.L. J.R.Thornton-Manning. and A.R.Dahl. (1998). Effect of cigarette smoke on CYP1A1, CYP1A2 and CYP2B1/2 of nasal mucosae in F344 rats. carcinogenesis. 19 (19), p655–662.
Whetstine, Johnathan R (2010). Handbook of Cell Signalling. 2nd ed. Cambridge: Academic Press. p2389-2397.
Wongtrakoongate, Patompon. (2015). Epigenetic therapy of cancer stem and progenitor cells by targeting DNA methylation machineries. World Journal of Stem Cells. 7 (1), p137-148.
Youn, A. Kim, K. Rabadan, R. Tycko, B. Shen Y. Wang S. (2018). A pan-cancer analysis of driver gene mutations, DNA methylation and gene expressions reveal that chromatin remodeling is a major mechanism inducing global changes in cancer epigenomes. BMC Medical genomics. 11 (1), p19.
Yunlong, Ma. and Ming D, Li. (2017). Establishment of a Strong Link Between Smoking and Cancer Pathogenesis through DNA Methylation Analysis. Scientific Report. 7 (1), p1811.
Zdenko, Herceg. and Thomas, Vaissière. (2011). Epigenetic mechanisms and cancer: An interface between the environment and the genome. Epigenetics. 6 (7), p 804-819.
Zhang H, Cai B. (2003). The impact of tobacco on lung health in China. Respirology. 8 (1), p17-21.
Zhang, Q., Spears, E., Boone, D. N., Li, Z., Gregory, M. A., & Hann, S. R. (2012). Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity. Proceedings of the National Academy of Sciences of the United States of America, 110(3), p978-983.
Charles S. Dela Cruz, MD, PhD, Lynn T. Tanoue, MD, and Richard A. Matthay, MD. (2011). Lung Cancer: Epidemiology, Etiology, and Prevention. Clinics in Chest Medicine. 32 (4), doi: [10.1016/j.ccm.2011.09.001].
Chen, Rong-Jane .Chang,Louis W. Lin, Pinpin .and Wang, Ying-Jan . (2011). Epigenetic Effects and Molecular Mechanisms of Tumorigenesis Induced by Cigarette Smoke: An Overview. Journal of oncology. 2011 (654931), p14.
Chen, T. Li, E. (2006). Establishment and maintenance of DNA methylation patterns in mammals. currents topic in microbiology and immunology. 301 (1), p179-201.
Costelloa, Joseph F., and Plass, Christoph . (2001). Methylation matters . Journal of Medical Genetic. 38 (5), p285-303.Aniruddha, Chatterjee. Euan, J Rodgera.Eccles, Michael R. (2018). Epigenetic drivers of tumourigenesis and cancer metastasis. Seminars in cancer biology. 51 (1), p149-159.
Debina Sarkar, Euphemia Y Leung, Bruce C Baguley, Graeme J Finlay & Marjan E Askarian-Amiri. (2015). Epigenetic regulation in human melanoma: past and future. Epigenetics. 10 (2), p 103-121.
Diane E. Handy, PhD, Rita Castro, PhD, and Joseph Loscalzo, MD, PhD. (2011). Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular Disease. Circulation. 123 (19), p2145-2156.
Flotho, C. Claus, R. Batz, C. Schneider, M. Sandrock, I. Ihde, S. Plass, C. Niemeyer, C. M. & Lübbert, M . (2009). The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. 23 (1), p1019–1028.
Ghavifekr Fakhr, M., Farshdousti Hagh, M., Shanehbandi, D., & Baradaran, B. (2013). DNA methylation pattern as important epigenetic criterion in cancer. Genetics research international, 2013(1), p317569.
Handy, PhD,Diane E.Castro, PhD,Rita.and Loscalzo, MD, PhD,Joseph. . (2012). Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular Disease. Circulation. 123 (19), p2145–2156.
Hecht S. S. (2014). It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco. Cancer prevention research (Philadelphia, Pa.), 7(7), p639-47.
Hirota T. (2018). Epigenetic Regulation of Pharmacokinetic-related Genes in Human Tissues. Yakugaku Zasshi. 138 (11), p1391-1396.
Huyn, Nam Cong-Nhat.Everts, Vincent.Ampornaramveth, Ruchanee Salingcarnboriboon.. (2017). Histone deacetylases and their roles in mineralized tissue regeneration. Bone Reports. 7 (1), p33-40.
Irvine, Ryan A. Lin,Iping G. and Hsieh, Chih-Lin. (2002). DNA Methylation Has a Local Effect on Transcription and Histone Acetylation. Molecular and Cellular Biology. 22 (19), p6689–6696.
Jin, Lihua. Hanigan, Christin L. Wu, Yu. Wang, Wei. Park, Ben Ho. Woster, Patrick M. and Robert A. Casero, Jr. (2013). Loss of LSD1 (lysine-specific demethylase 1) suppresses growth and alters gene expression of human colon cancer cells in a p53- and DNMT1(DNA methyltransferase 1)-independent manner. Biochemical Journal. 449 (2), p459-468.
Jin, Zhaohui. Gao, Fengqin. Flagg, Tammy. and Deng, Xingming. (2004). Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation.. The Journal of Biological Chemistry. 279 (38), p40209-40219.
Jones, P. A., & Liang, G. (2009). Rethinking how DNA methylation patterns are maintained. Nature reviews. Genetics 10(11). p805-11.
Jyoti Malhotra, Matteo Malvezzi, Eva Negri, Carlo La Vecchia, Paolo Boffetta. (2016). Risk factors for lung cancer worldwide. European Respiratory Journal. 52 (5), p40.
Kazanets, Anna. Shorstova, Tatiana. Hilmi, Khalid.Marques, Maud. Witcher, Michael. (2016). Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1865 (2), p275-288.
Kim, J. A., & Yeom, Y. I. (2017). Metabolic Signaling to Epigenetic Alterations in Cancer. Biomolecules & therapeutics, 26(1), p69-80.
Lawrence, Moyra.Daujat, Sylvain.Schneider,Robert . (2016). Lateral Thinking: How Histone Modifications Regulate Gene Expression. Trend in Genetic. 32 (1), p42-56.
Lin., Ruo-Kai. Hsieh., Yi-Shuan. Lin., Pinpin. Hsu., Han-Shui. Chen.,Chih-Yi. Tang.,Yen-An. Lee., Chung-Fan. and Wang., Yi-Ching. (2010). The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor suppressor gene hypermethylation in mice and lung cancer patients. J Clin Invest. 120 (2), p521–532.
Lopez-Serra, L. Esteller, M. (2008). Proteins that bind methylated DNA and human cancer: reading the wrong words. British Journal of Cancer. 98 (12), p1881-1885.
McKeown S. R. (2014). Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. The British journal of radiology, 87(1035), p20130676.
Meng,Min. Zhao, Xin-Han. Ning, Qian. Hou, Lei. Xin, Guo-Hong. and Liu, Li-Feng . (2012). Tumor stem cells: A new approach for tumor therapy . Oncology Letters. 4 (2), p187-193.
Moore, L. D., Le, T., & Fan, G. (2012). DNA methylation and its basic function. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 38(1), p23-38.
Muz, B., de la Puente, P., Azab, F., & Azab, A. K. (2015). The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckland, N.Z.), 3(1), p83-92.
Nan, Xinsheng Ng, Huck-Hui Johnson, Colin A. Laherty, Carol D. Turner, Bryan M. Eisenman, Robert N. and Bird, Adrian. (1998). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 393 (1), p386-389.
Nivedita, Chatterjee. Jiwan, Gim. and Jinhee, Choi. (2018). Epigenetic profiling to environmental stressors in model and non-model organisms: Ecotoxicology perspective. Environemental health and toxicology. 33 (3), p e2018015.
Nyström, Minna. and Mutanen, Marja. (2009). Diet and epigenetics in colon cancer. World Journal of Gastroenterology. 15 (3), p257-263.
Ovesen, Jerald. Puga, Alvaro.Schnekenburger, Michael. (2011). Aryl Hydrocarbon Receptor Ligands of Widely Different Toxic Equivalency Factors Induce Similar HistoneMarksin Target Gene Chromatin. Toxicological Sciences. 121 (1), p123-131.
Parascandola, M. (2004). Skepticism, statistical methods, and the cigarette: a historical analysis of a methodological debate. Perspective in Biology and Medicine. 47 (2), p244-261.
Peter W. Laird. (2003). Review Article | Published: 01 April 2003 Early detection The the promise of DNA methylation markers. Nature Reviews Cancer. 3 (1), p253–266.
Peterson, Lisa A. (2017). Context Matters: Contribution of Specific DNA Adducts to the Genotoxic Properties of the Tobacco-Specific Nitrosamine NNK. Chemical Research in Toxicology. 30 (1), p 420–433.
Philibert, R. A., Beach, S. R., & Brody, G. H. (2014). The DNA methylation signature of smoking: an archetype for the identification of biomarkers for behavioral illness. Nebraska Symposium on Motivation. Nebraska Symposium on Motivation, 61, 109-27.
Ransohoff, J. D., Wei, Y., & Khavari, P. A. (2017). The functions and unique features of long intergenic non-coding RNA. Nature reviews. Molecular cell biology, 19(3), 143-157.
Reamon-Buettner, SM. Mutschler, V. Borlak, J. (2008). The next innovation cycle in toxicogenomics: environmental epigenetics. Mutation research. 659 (1-2), p158-165.
Sánchez-Pernaute, Olga. (2017). Epigenetic therapies, still in the midway between facts and fiction. Reumatologia Clinica. 13 (6), p311-370.
Schiffmann, Insa. Greve, Gabriele. Jung, Manfred. and Lübberta, Michael . (2016). Epigenetic therapy approaches in non-small cell lung cancer: Update and perspectives. Epigenetics. 11 (12), p858–870.
Schulz, W.A. Steinhoff, C. Florl, AR. (2006). Methylation of endogenous human retroelements in health and disease. currents topic in microbiology and immunology. 310 (1), p211-250.
Scott M. Langevin, Robert A. Kratzke, and Karl T. Kelsey. (2016). Epigenetics of Lung Cancer. Transl Res. 165 (1), p74-90.
Seaberg, R. M.; Van Der Kooy, D. (2003). "Stem and progenitor cells: The premature desertion of rigorous definitions". Trends in Neuroscience. 26 (3), p125-131.
Severin, P. M., Zou, X., Gaub, H. E., & Schulten, K. (2011). Cytosine methylation alters DNA mechanical properties. Nucleic acids research, 39(20), p8740-51.
Shi L, Zheng M, Hou J, Zhu B, Wang X. (2016). Regulatory roles of epigenetic modulators, modifiers and mediators in lung cancer. Seminars in cancer biology. 42 (3), p4-12.
Shih, Yin-Hwa. Shieh, Tzong-Ming. (2017). Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers. International Journal of Molecular Science. 18 (6), p1210.
Shikhar Sharma, Theresa K. Kelly, Peter A. Jones. (2010). Epigenetics in cancer. carcinogenesis. 31 (1), p27–36.
Singh, Sandeep. Chellappana, Srikumar. (2014). Lung cancer stem cells: Molecular features and therapeutic targets. Molecular Aspects of Medicine. 39 (1), p50-60.
Steinberg S. F. (2012). Regulation of protein kinase D1 activity. Molecular pharmacology, 81(3), p284-291.
Struhl K. (2014). Is DNA methylation of tumour suppressor genes epigenetic?. eLife. 3(1). p e02475.
Suarez-Ulloa V, Gonzalez-Romero R, Eirin-Lopez J.M. (2015). Environmental epigenetics: A promising venue for developing next-generation pollution biomonitoring tools in marine invertebrates. Marine Pollution Bulletin. 98 (1-2), p5-13.
Subramaniam, Dharmalingam. Thombre, Ravi. Dhar, Animesh. and Anant, Shrikant. (2014). DNA Methyltransferases: A Novel Target for Prevention and Therapy. Front Oncol. 4 (80), [doi: 10.3389/fonc.2014.00080].
Svedruži?, Željko M.and Reich, Norbert O. (2005). DNA Cytosine C5 Methyltransferase Dnmt1:? Catalysis-Dependent Release of Allosteric Inhibition. Biochemistry. 44 (27), p9472–9485.
Tarang, S., Kumar, S., & Batra, S. K. (2012). Mucins and toll-like receptors: kith and kin in infection and cancer. Cancer letters, 321(2), p110-9.
Tong-Hong Wang, Shih-Min Hsia, Yin-Hwa Shih, and Tzong-Ming Shieh 8. (2017). Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers. International Journal of Molecular Science. 18 (6), doi:10.3390/ijms18061210.
Verma M. (2015). Toxicoepigenomics and cancer: implications for screening. Methods in Molecular Biology. 1238 (1), p355-367.
Wang, Yan.Sun, ZhongSheng. and Szyf, Moshe. (2017). S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells. Oncotarget. 8 (67), p111866–111881.
Wardlaw, S.A. Nikula,K.J. Kracko, D.A. Finch,G.L. J.R.Thornton-Manning. and A.R.Dahl. (1998). Effect of cigarette smoke on CYP1A1, CYP1A2 and CYP2B1/2 of nasal mucosae in F344 rats. carcinogenesis. 19 (19), p655–662.
Whetstine, Johnathan R (2010). Handbook of Cell Signalling. 2nd ed. Cambridge: Academic Press. p2389-2397.
Wongtrakoongate, Patompon. (2015). Epigenetic therapy of cancer stem and progenitor cells by targeting DNA methylation machineries. World Journal of Stem Cells. 7 (1), p137-148.
Youn, A. Kim, K. Rabadan, R. Tycko, B. Shen Y. Wang S. (2018). A pan-cancer analysis of driver gene mutations, DNA methylation and gene expressions reveal that chromatin remodeling is a major mechanism inducing global changes in cancer epigenomes. BMC Medical genomics. 11 (1), p19.
Yunlong, Ma. and Ming D, Li. (2017). Establishment of a Strong Link Between Smoking and Cancer Pathogenesis through DNA Methylation Analysis. Scientific Report. 7 (1), p1811.
Zdenko, Herceg. and Thomas, Vaissière. (2011). Epigenetic mechanisms and cancer: An interface between the environment and the genome. Epigenetics. 6 (7), p 804-819.
Zhang H, Cai B. (2003). The impact of tobacco on lung health in China. Respirology. 8 (1), p17-21.
Zhang, Q., Spears, E., Boone, D. N., Li, Z., Gregory, M. A., & Hann, S. R. (2012). Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity. Proceedings of the National Academy of Sciences of the United States of America, 110(3), p978-983.
