Experimental investigations of carcinogen-induced mutation spectra: Innovation, challenges and future directions.

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Pamela N MelkiJiri Zavadil

Abstract

Recent years have witnessed an expansion of mutagenesis research focusing on experimentally modeled genome-scale mutational signatures of carcinogens and of endogenous processes. Experimental mutational signatures can explain etiologic links to patterns found in human tumors that may be linked to same exposures, and can serve as biomarkers of exposure history and may even provide insights on causality. A number of innovative exposure models have been employed and reported, based on cells cultured in monolayers or in 3-D, on organoids, induced pluripotent stem cells, non-mammalian organisms, microorganisms and rodent bioassays. Here we discuss some of the latest developments and pros and cons of these experimental systems used in mutational signature analysis. Integrative designs that bring together multiple exposure systems (in vitro, in vivo and in silico pan-cancer data mining) started emerging as powerful tools to identify robust mutational signatures of the tested cancer risk agents. We further propose that devising a new generation of cell-based models is warranted to streamline systematic testing of carcinogen effects on the cell genomes, while seeking to increasingly supplant animal with non-animal systems to address rel...Continue Reading

References

Apr 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·M R Stampfer, J C Bartley
Feb 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Zhipei LiuMonica Hollstein
Mar 3, 2004·Nature Reviews. Cancer·P Andrew FutrealMichael R Stratton
Jan 16, 2013·Cell Reports·Ludmil B AlexandrovMichael R Stratton
Aug 9, 2013·Science Translational Medicine·Song Ling PoonBin Tean Teh
Mar 29, 2014·Scientific Reports·Magali OlivierJiri Zavadil
Dec 2, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Paul L SeversonBernard W Futscher
May 6, 2015·Trends in Genetics : TIG·Romulo SegoviaPeter C Stirling
Nov 26, 2015·Environmental Health Perspectives·Martyn T SmithKurt Straif
May 3, 2016·Nature Communications·Sandro MorganellaSerena Nik-Zainal
May 11, 2016·Genome Biology·Bernadett SzikrisztDávid Szüts
May 11, 2016·Environmental Health Perspectives·Neela GuhaDinesh Kumar Barupal
Oct 5, 2016·Nature·Francis BlokzijlRuben van Boxtel
Oct 19, 2016·Basic & Clinical Pharmacology & Toxicology·Maria ZhivaguiJiri Zavadil
Jun 22, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sreenivasa C RamaiahgariStephen S Ferguson
Jul 26, 2017·Genome Research·Mi Ni HuangSteven G Rozen
May 3, 2018·Nature Communications·Xueqing ZouSerena Nik-Zainal
Sep 17, 2018·Journal of Hematology & Oncology·Hanxiao XuKongming Wu
Oct 6, 2018·Proceedings of the National Academy of Sciences of the United States of America·Michelle DowJoan Font-Burgada
Oct 20, 2018·Science·Iñigo MartincorenaPhilip H Jones
Dec 7, 2018·Chemical Research in Toxicology·Kathryn Z GuytonMartyn T Smith
Mar 23, 2019·Cell·Abel Gonzalez-PerezNuria Lopez-Bigas
Apr 16, 2019·Cell·Jill E KucabSerena Nik-Zainal
Apr 22, 2019·The Lancet Oncology·UNKNOWN IARC Monographs Priorities Group
Sep 12, 2019·Chemical Research in Toxicology·Jiri Zavadil, Steven G Rozen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.