[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331340-105":59,"doc-detail-331340-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","forwardreverse-mutation-cycles-in-cancer-cell-lines-under-chemical-treatments","Forward–reverse mutation cycles in cancer cell lines under chemical treatments","","Spontaneous forward–reverse mutations previously observed in clinical cancer samples and HeLa cells are tested under chemical stimulation. Single nucleotide variants and copy number variants are measured in HeLa and A549 exposed to wogonin-containing medium or acidic medium. Wogonin induces mutation cycles on days 16–18, while acidic conditions trigger multiple cycles with different magnitudes. Colocalization suggests CNVs concentrate in expanded, unstable regions near promoters, histones, and non-coding transcription sites; cell morphology also changes during cycling. Chemical stresses promote cyclic mutations to differing extents.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/forwardreverse-mutation-cycles-in-cancer-cell-lines-under-chemical-treatments/331340/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/forwardreverse-mutation-cycles-in-cancer-cell-lines-under-chemical-treatments/331340.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-25","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What experimental conditions were used to study forward–reverse mutation cycles?","Question",{"text":112,"@type":113},"HeLa and A549 cells were exposed to a wogonin-containing medium or to an acidic medium to examine how chemical stimulation affects mutation cycling.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did wogonin and acidic medium differ in their mutation-cycle patterns?",{"text":117,"@type":113},"Wogonin induced mutation cycles in both cell lines during days 16–18, whereas acidic medium produced multiple mutation cycles with different magnitudes.",{"name":119,"@type":110,"acceptedAnswer":120},"What genomic features were associated with copy number variation during the mutation cycles?",{"text":121,"@type":113},"Genomic feature colocalization indicates that CNVs tend to occur in expanded and unstable regions and near promoters, histones, and non-coding transcription sites.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331340,1790146004,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41,"preview_page_count":4},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","Chen et al. Human Genomics (2024) 18:106 [https://doi.org/10.1186/s40246-024-00661-1](https://doi.org/10.1186/s40246-024-00661-1)  \nHuman Genomics  \n RESEARCH Open Access  \nForward–reverse mutation cycles in cancer   cell lines under chemical treatments  \nSi Chen1,2†, Iram S. Tyagi2†, Wai Kin Mat2, Muhammad A. Khan2, Weijian Fan2, Zhenggang Wu1,2,4, Taobo Hu2, Can Yang1,3* and Hong Xue1,2,4*  \nAbstract  \nSpontaneous forward–reverse mutations were reported by us earlier in clinical samples from various types of cancers and in HeLa cells under normal culture conditions. To investigate the effects of chemical stimulations on such mutation cycles, the present study examined single nucleotide variations (SNVs) and copy number variations (CNVs) in HeLa and A549 cells exposed to wogonin-containing or acidic medium. In wogonin, both cell lines showed a mutation cycle during days 16–18. In acidic medium, both cell lines displayed multiple mutation cycles of different magnitudes. Genomic feature colocalization analysis suggests that CNVs tend to occur in expanded and unstable regions, and near promoters, histones, and non-coding transcription sites. Moreover, phenotypic variations in cell morphology occurred during the forward–reverse mutation cycles under both types of chemical treatments. In conclusion, chemical stresses imposed by wogonin or acidity promoted cyclic forward–reverse mutations in both HeLa and A549 cells to different extents.  \nKeywords Acidic culture medium, AluScan, Anticancer agent, Cell morphology change, Cell cultures, Copy number variation, Genome instability, Next generation sequencing, Single nucleotide variation, Wogonin  \nIntroduction  \nCancer development has been investigated extensively at the molecular and genetic levels to better understand the dynamics of its progression, resistance to therapy, and biomarkers for risk stratification [1, 2]. While human  \n†Si Chen and Iram S. Tyagi are Co-first authors.  \n*Correspondence: Can Yang [macyang@ust.hk](macyang@ust.hk)[ ](macyang@ust.hk)Hong Xue [hxue@ust.hk](hxue@ust.hk)  \n1 Guangzhou HKUST Fok Ying Tung Research Institute, Science and Technology Building, Nansha Information Technology Park, Nansha, Guangzhou 511458, China  \n2 Division of Life Science and Center of Applied Genomics, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China  \n3 Department of Mathematics, Hong Kong University of Science and Technology, ClearWater Bay, Hong Kong, China  \n4 Center for Cancer Genomics, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China  \nmalignancies are thought to originate mostly from a single cell, most tumors show startling heterogeneity in genomic structure, cell morphology, proliferation rate, and metastatic potential by the time of diagnosis [3–5]. Genetic markers, including loss of heterozygosity (LOH), gain of heterozygosity (GOH), and copy number variation (CNV), have delineated some of the mutations that play important roles in the emergence and proliferation of invasive tumors [6–10], and studies have revealed the important role of heterogeneity within tumors that would lead to the appearance of subclones with a fitness advantage in malignancies ranging from hematopoietic cancers to different types of solid tumors [11–14], resulting in the basic hallmarks of cancer: sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, induction of angiogenesis, and activation of invasiveness and metastasis [15]. Morphologically, the evolution from hyperplasia or dysplasia to neoplasia and malignant neoplasia has long been  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and ","cbCaistxR7juTDyv","https://ap.wps.com/l/cbCaistxR7juTDyv","pdf",3646705,12,"English","# Abstract\n# Introduction","[{\"question\":\"What experimental conditions were used to study forward–reverse mutation cycles?\",\"answer\":\"HeLa and A549 cells were exposed to a wogonin-containing medium or to an acidic medium to examine how chemical stimulation affects mutation cycling.\"},{\"question\":\"How did wogonin and acidic medium differ in their mutation-cycle patterns?\",\"answer\":\"Wogonin induced mutation cycles in both cell lines during days 16–18, whereas acidic medium produced multiple mutation cycles with different magnitudes.\"},{\"question\":\"What genomic features were associated with copy number variation during the mutation cycles?\",\"answer\":\"Genomic feature colocalization indicates that CNVs tend to occur in expanded and unstable regions and near promoters, histones, and non-coding transcription sites.\"}]","Forward–reverse mutation cycles in cancer cell lines under chemical treatments | PDF",1789992736]