scholarly journals Mutational signatures associated with exposure to carcinogenic microplastic compounds bisphenol A and styrene oxide

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Xiaoju Hu ◽  
Antara Biswas ◽  
Anchal Sharma ◽  
Halle Sarkodie ◽  
Ivy Tran ◽  
...  
Keyword(s):  
Public Health ◽  
Bisphenol A ◽  
Styrene Oxide ◽  
Systematic Evaluation ◽  
Cancer Type ◽  
Mutational Signatures ◽  
Cellular Processes ◽  
Genome Wide ◽  
Cancer Genomes ◽  
Environmental Agents

Abstract Microplastic pollutants in oceans and food chains are concerning to public health. Common plasticizing compounds Bisphenol-A (BPA) and Styrene-7,8-Oxide (SO) are now labeled as carcinogens. We show that BPA and SO cause deoxyribonucleic acid damage and mutagenesis in human cells, and analyze the genome-wide point mutation and genomic rearrangement patterns associated with BPA and SO exposure. A subset of the single- and doublet base substitutions shows mutagenesis near or at guanine, consistent with these compounds’ preferences to form guanosine adducts. Presence of other mutational signatures suggest additional mutagenesis probably due to complex effects of BPA and SO on diverse cellular processes. Analyzing data for 19 cancer cohorts, we find that tumors of digestive and urinary organs show relatively high similarity in mutational profiles, and the burden of such mutations increases with age. Even within the same cancer type, proportions of corresponding mutational patterns vary among the cohorts from different countries, as does the amount of microplastic waste in ocean waters. BPA and SO are relatively mild mutagens, and other environmental agents can also potentially generate similar, complex mutational patterns in cancer genomes. Nonetheless, our findings call for systematic evaluation of public health consequences of microplastic exposure worldwide.

scholarly journals DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Benjamin JM Taylor ◽  
Serena Nik-Zainal ◽  
Yee Ling Wu ◽  
Lucy A Stebbings ◽  
Keiran Raine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Abasic Site ◽  
Dna Breaks ◽  
Mutational Signatures ◽  
Genome Wide ◽  
Cancer Genomes ◽  
Strand Breakage ◽  
Cytidine Deamination ◽  
Apobec Family ◽  
Insight Into

Breast cancer genomes have revealed a novel form of mutation showers (kataegis) in which multiple same-strand substitutions at C:G pairs spaced one to several hundred nucleotides apart are clustered over kilobase-sized regions, often associated with sites of DNA rearrangement. We show kataegis can result from AID/APOBEC-catalysed cytidine deamination in the vicinity of DNA breaks, likely through action on single-stranded DNA exposed during resection. Cancer-like kataegis can be recapitulated by expression of AID/APOBEC family deaminases in yeast where it largely depends on uracil excision, which generates an abasic site for strand breakage. Localized kataegis can also be nucleated by an I-SceI-induced break. Genome-wide patterns of APOBEC3-catalyzed deamination in yeast reveal APOBEC3B and 3A as the deaminases whose mutational signatures are most similar to those of breast cancer kataegic mutations. Together with expression and functional assays, the results implicate APOBEC3B/A in breast cancer hypermutation and give insight into the mechanism of kataegis.

Magnetite Doped Metal-Organic Framework Nanocomposites: An Efficient Adsorbent for Removal of Bisphenol-A Pollutant

2021 ◽  
Author(s):  
Okan Icten ◽  
Demet Ozer
Keyword(s):  
Public Health ◽  
Bisphenol A ◽  
Toxic Effect ◽  
Metal Organic Framework ◽  
Aqueous Environment ◽  
Metal Organic ◽  
Efficient Adsorbent ◽  
Organic Framework

The removal of bisphenol-A (BPA) from the aqueous environment is a vital issue for public health due to its toxic effect. In this work, variable amounts of the dextran coated-magnetite...

scholarly journals Lineage-defined leiomyosarcoma subtypes emerge years before diagnosis and determine patient survival

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nathaniel D. Anderson ◽  
Yael Babichev ◽  
Fabio Fuligni ◽  
Federico Comitani ◽  
Mehdi Layeghifard ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Therapeutic Strategy ◽  
Genetic Factors ◽  
Phylogenetic Reconstruction ◽  
Mutational Signatures ◽  
Multiple Tumor ◽  
Dystrophin Expression ◽  
Genome Wide ◽  
Damage Response ◽  
Disease Site

AbstractLeiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyze 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlight the very early origins of LMS. We uncover three specific subtypes of LMS that likely develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynecological origin harbor genomic dystrophin deletions and/or loss of dystrophin expression, acquire the highest burden of genomic mutation, and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP trappers and other DNA damage response inhibitors, suggesting a promising therapeutic strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis.

scholarly journals Prediction of genome-wide effects of single nucleotide variants on transcription factor binding

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sebastian Carrasco Pro ◽  
Katia Bulekova ◽  
Brian Gregor ◽  
Adam Labadorf ◽  
Juan Ignacio Fuxman Bass
Keyword(s):  
Binding Sites ◽  
Cancer Type ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Gene Regulatory ◽  
The Impact ◽  
The Relationship

Abstract Single nucleotide variants (SNVs) located in transcriptional regulatory regions can result in gene expression changes that lead to adaptive or detrimental phenotypic outcomes. Here, we predict gain or loss of binding sites for 741 transcription factors (TFs) across the human genome. We calculated ‘gainability’ and ‘disruptability’ scores for each TF that represent the likelihood of binding sites being created or disrupted, respectively. We found that functional cis-eQTL SNVs are more likely to alter TF binding sites than rare SNVs in the human population. In addition, we show that cancer somatic mutations have different effects on TF binding sites from different TF families on a cancer-type basis. Finally, we discuss the relationship between these results and cancer mutational signatures. Altogether, we provide a blueprint to study the impact of SNVs derived from genetic variation or disease association on TF binding to gene regulatory regions.

scholarly journals Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures

Epigenomes ◽  
2018 ◽  
Vol 2 (3) ◽  
pp. 13
Author(s):  
José Belizário
Keyword(s):  
Stem Cells ◽  
Skeletal Muscles ◽  
Small Population ◽  
Epigenetic Mechanisms ◽  
Cancer Risks ◽  
Mutational Signatures ◽  
Environmental Agents ◽  
Risk Of Malignancy ◽  
The Brain ◽  
Cellular Genome

Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting.

scholarly journals Communicating With Residents About Risks Following the Fukushima Nuclear Accident

2017 ◽  
Vol 29 (2_suppl) ◽  
pp. 74S-89S ◽  
Author(s):  
Michio Murakami ◽  
Akiko Sato ◽  
Shiro Matsui ◽  
Aya Goto ◽  
Atsushi Kumagai ◽  
...  
Keyword(s):  
Public Health ◽  
Risk Communication ◽  
Health Management ◽  
Well Being ◽  
Lessons Learned ◽  
Nuclear Accident ◽  
Fukushima Nuclear Accident ◽  
Whole Body ◽  
Systematic Evaluation ◽  
Medical Professionals

The Fukushima nuclear accident in March 2011 posed major threats to public health. In response, medical professionals have tried to communicate the risks to residents. To investigate forms of risk communication and to share lessons learned, we reviewed medical professionals’ activities in Fukushima Prefecture from the prefectural level to the individual level: public communication through Fukushima Health Management Surveys, a Yorozu (“general”) health consultation project, communications of radiological conditions and health promotion in Iitate and Kawauchi villages, dialogues based on whole-body counter, and science communications through online media. The activities generally started with radiation risks, mainly through group-based discussions, but gradually shifted to face-to-face communications to address comprehensive health risks to individuals and well-being. The activities were intended to support residents’ decisions and to promote public health in a participatory manner. This article highlights the need for a systematic evaluation of ongoing risk communication practices, and a wider application of successful approaches for Fukushima recovery and for better preparedness for future disasters.

scholarly journals Chromatin architectural proteins regulate flowering time by precluding gene looping

2021 ◽  
Vol 7 (24) ◽  
pp. eabg3097
Author(s):  
Bo Zhao ◽  
Yanpeng Xi ◽  
Junghyun Kim ◽  
Sibum Sung
Keyword(s):  
Chromatin Structure ◽  
Cellular Processes ◽  
Genome Wide ◽  
A Genome ◽  
Evolutionarily Conserved ◽  
Architectural Proteins ◽  
Floral Repressor ◽  
Flanking Regions ◽  
Genome Wide Study

Chromatin structure is critical for gene expression and many other cellular processes. In Arabidopsis thaliana, the floral repressor FLC adopts a self-loop chromatin structure via bridging of its flanking regions. This local gene loop is necessary for active FLC expression. However, the molecular mechanism underlying the formation of this class of gene loops is unknown. Here, we report the characterization of a group of linker histone-like proteins, named the GH1-HMGA family in Arabidopsis, which act as chromatin architecture modulators. We demonstrate that these family members redundantly promote the floral transition through the repression of FLC. A genome-wide study revealed that this family preferentially binds to the 5′ and 3′ ends of gene bodies. The loss of this binding increases FLC expression by stabilizing the FLC 5′ to 3′ gene looping. Our study provides mechanistic insights into how a family of evolutionarily conserved proteins regulates the formation of local gene loops.

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