International Journal of Molecular Sciences Chemically- Induced DNA Damage, Mutagenesis, and Cancer Edited by Ashis K. Basu and Takehiko Nohmi Printed Edition of the Special Issue Published in IJMS www.mdpi.com/journal/ijms Chemically-Induced DNA Damage, Mutagenesis, and Cancer Chemically-Induced DNA Damage, Mutagenesis, and Cancer Special Issue Editors Ashis K. Basu Takehiko Nohmi MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade Special Issue Editors Ashis K. Basu Takehiko Nohmi University of Connecticut National Institute of Health Sciences USA Japan Editorial Office MDPI St. Alban-Anlage 66 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal International Journal of Molecular Sciences (ISSN 1422-0067) from 2017 to 2018 (available at: http:// www.mdpi.com/journal/ijms/special issues/chemical induced mutagenesis) For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03897-129-0 (Pbk) ISBN 978-3-03897-130-6 (PDF) Articles in this volume are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book taken as a whole is c 2018 MDPI, Basel, Switzerland, distributed under the terms and conditions of the Creative Commons license CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). Contents About the Special Issue Editors ..................................... vii Preface to ”Chemically-Induced DNA Damage, Mutagenesis, and Cancer” ............ ix Ashis K. Basu DNA Damage, Mutagenesis and Cancer Reprinted from: Int. J. Mol. Sci. 2018, 19, 970, doi: 10.3390/ijms19040970 .............. 1 Peter W. Villalta and Silvia Balbo The Future of DNA Adductomic Analysis Reprinted from: Int. J. Mol. Sci. 2017, 18, 1870, doi: 10.3390/ijms18091870 .............. 14 Riccardo Miggiano, Anna Valenti, Franca Rossi, Menico Rizzi, Giuseppe Perugino and Maria Ciaramella Every OGT Is Illuminated ... by Fluorescent and Synchrotron Lights Reprinted from: Int. J. Mol. Sci. 2017, 18, 2613, doi: 10.3390/ijms18122613 .............. 34 Anna Kakehashi, Naomi Ishii, Takahiro Okuno, Masaki Fujioka, Min Gi and Hideki Wanibuchi Enhanced Susceptibility of Ogg1 Mutant Mice to Multiorgan Carcinogenesis Reprinted from: Int. J. Mol. Sci. 2017, 18, 1801, doi: 10.3390/ijms18081801 .............. 52 Elizaveta O. Boldinova, Paulina H. Wanrooij, Evgeniy S. Shilkin, Sjoerd Wanrooij and Alena V. Makarova DNA Damage Tolerance by Eukaryotic DNA Polymerase and Primase PrimPol Reprinted from: Int. J. Mol. Sci. 2017, 18, 1584, doi: 10.3390/ijms18071584 .............. 69 Neenu Singh, Bryant C. Nelson, Leona D. Scanlan, Erdem Coskun, Pawel Jaruga and Shareen H. Doak Exposure to Engineered Nanomaterials: Impact on DNA Repair Pathways Reprinted from: Int. J. Mol. Sci. 2017, 18, 1515, doi: 10.3390/ijms18071515 .............. 83 Filippo Cellai, Armelle Munnia, Jessica Viti, Saer Doumett, Costanza Ravagli, Elisabetta Ceni, Tommaso Mello, Simone Polvani, Roger W. Giese, Giovanni Baldi, Andrea Galli and Marco E. M. Peluso Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells Reprinted from: Int. J. Mol. Sci. 2017, 18, 939, doi: 10.3390/ijms18050939 .............. 98 Jeong-Hyeon Ko, Gautam Sethi, Jae-Young Um, Muthu K Shanmugam, Frank Arfuso, Alan Prem Kumar, Anupam Bishayee and Kwang Seok Ahn The Role of Resveratrol in Cancer Therapy Reprinted from: Int. J. Mol. Sci. 2017, 18, 2589, doi: 10.3390/ijms18122589 ..............113 Hong-Mei Yang, Chao-Yue Sun, Jia-Li Liang, Lie-Qiang Xu, Zhen-Biao Zhang, Dan-Dan Luo, Han-Bin Chen, Yong-Zhong Huang, Qi Wang, David Yue-Wei Lee, Jie Yuan and Yu-Cui Li Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice Reprinted from: Int. J. Mol. Sci. 2017, 18, 465, doi: 10.3390/ijms18030465 ..............149 v Razmik Mirzayans, Bonnie Andrais, Piyush Kumar and David Murray Significance of Wild-Type p53 Signaling in Suppressing Apoptosis in Response to Chemical Genotoxic Agents: Impact on Chemotherapy Outcome Reprinted from: Int. J. Mol. Sci. 2017, 19, 928, doi: 10.3390/ijms18050928 ..............164 Tze-An Yuan, Vandy Yourk, Ali Farhat, Argyrios Ziogas, Frank L. Meyskens, Hoda Anton-Culver and Feng Liu-Smith A Case-Control Study of the Genetic Variability in Reactive Oxygen Species—Metabolizing Enzymes in Melanoma Risk Reprinted from: Int. J. Mol. Sci. 2018, 19, 242, doi: 10.3390/ijms19010242 ..............184 Xiali Zhong, Xing Yi, Rita de C´assia da Silveira e S´a, Yujing Zhang, Kaihua Liu, Fang Xiao and Caigao Zhong CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI) Toxicity Reprinted from: Int. J. Mol. Sci. 2017, 18, 816, doi: 10.3390/ijms18040816 ..............202 Guochao Liu, Hui Wang, Fengmei Zhang, Youjia Tian, Zhujun Tian, Zuchao Cai, David Lim and Zhihui Feng The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats Reprinted from: Int. J. Mol. Sci. 2017, 18, 1027, doi: 10.3390/ijms18051027 ..............222 Markus Wirth, Daniel Jira, Armin Ott, Guido Piontek and Anja Pickhard High NOTCH1 mRNA Expression Is Associated with Better Survival in HNSCC Reprinted from: Int. J. Mol. Sci. 2018, 19, 830, doi: 10.3390/ijms19030830 ..............235 Suleva Povea-Cabello, Manuel Oropesa-Avila,´ Patricia de la Cruz-Ojeda, Marina Villanueva-Paz, Mario de la Mata, Juan Miguel Su´arez-Rivero, M´onica Alvarez-C´´ ordoba, Irene Villal´on-Garc´ıa, David Cot´an, Patricia Ybot-Gonz´alez and Jos´eA.S´anchez-Alc´azar Dynamic Reorganization of the Cytoskeleton during Apoptosis: The Two Coffins Hypothesis Reprinted from: Int. J. Mol. Sci. 2017, 18, 2393, doi: 10.3390/ijms18112393 ..............248 vi About the Special Issue Editors Ashis Basu, Ph.D., is Professor of Chemistry at the University of Connecticut. The research focus of the Basu laboratory is the determination of the consequences of DNA damaged by anti-tumor drugs, chemical carcinogens, oxidation, or radiation. This research at the interface of chemistry and biology involves the introduction of specific lesions in DNA by organic synthesis, investigation of the structural effects of the lesions using biophysical methods, and studying their repair and replication. Takehiko Nohmi, Ph.D., became a staff scientist at the National Institute of Health Sciences (NIHS), Tokyo in 1978. He was a postdoctoral fellow/associate at the Massachusetts Institute of Technology (MIT) (1986 to 1988). After returning to Japan, he became a section chief in 1989 and the Head of the Division of Genetics and Mutagenesis, NIHS, in 2008. He developed Salmonella typhimurium YG1021 and YG1024, strains which are highly sensitive to environmental mutagens, and gpt delta transgenic mice/rats for in vivo mutagenesis. He was involved in the discovery of novel DNA polymerase DinB, a prototype of Y-family DNA polymerase. He received the JEMS award and annual award from the Japanese Environmental Mutagen Society (JEMS) in 2006 and 1992, respectively. He was the President of the International Association of Environmental Mutagenesis and Genomics Societies (IAEMGS, 2013–2017). He retired from NIHS (Tokyo) in 2012 and is currently a scientist emeritus and a visiting scientist at NIHS (Tokyo). vii Preface to ”Chemically-Induced DNA Damage, Mutagenesis, and Cancer” This volume provides a snapshot of the current advances in chemical carcinogenesis. It promotes the view that DNA damage is an important first step in the process of carcinogenesis. DNA repair processes are active in every cell to correct these damages, yet the replication of damaged DNA may occur prior to repair, resulting in gene mutations and the generation of altered proteins. Mutations in an oncogene, a tumor-suppressor gene, or a gene that controls the cell cycle give rise to a clonal cell population with an advantage in proliferation. The complex process of carcinogenesis includes many such events, but has generally been considered to comprise the three main stages known as initiation, promotion, and progression, which ultimately give rise to the induction of human cancer. Fifteen articles published in a Special Issue of IJMS entitled “Chemically-Induced DNA Damage, Mutagenesis, and Cancer” provide an overview on the topic of the “consequence of DNA damage” in the context of human cancer with their challenges and highlights. The topics of the published articles cover a wide range, which include study of DNA adducts, DNA polymerase, DNA repair and repair defects, nanoparticle-induced DNA damage and cell death, metal toxicity, apoptosis, risk of melanoma, chemoprevention, a radiosensitizer for primary culture tumor cells, the signaling of a tumor suppressor gene, and an adjuvant for chemotherapy. The variety of articles published in this Special Issue underscores the diversity of this field of research. Evidently, this is only a glimpse of this very large area of research that includes thousands of active researchers working in many complementary directions to better understand the etiology of cancer and develop superior strategies for chemoprevention