High-throughput sequencing in mutation detection: A new generation of genotoxicity tests?

Abstract

The advent of next generation sequencing (NGS) technology has provided the means to directly analyze the genetic material in primary cells or tissues of any species in a high throughput manner for mutagenic effects of potential genotoxic agents. In principle, direct, genome-wide sequencing of human primary cells and/or tissue biopsies would open up opportunities to identify individuals possibly exposed to mutagenic agents, thereby replacing current risk assessment procedures based on surrogate markers and extrapolations from animal studies. NGS-based tests can also precisely characterize the mutation spectra induced by genotoxic agents, improving our knowledge of their mechanism of action. Thus far, NGS has not been widely employed in genetic toxicology due to the difficulties in measuring low-abundant somatic mutations. Here, we review different strategies to employ NGS for the detection of somatic mutations in a cost-effective manner and discuss the potential applicability of these methods in testing the mutagenicity of genotoxic agents.

Do DNA Double-Strand Breaks Drive Aging?

“…By extrapolating from the 3000 bp reporter locus to the genome overall, genome rearrangements in the mouse heart were estimated to increase with age to about 40 rearrangements per cardiomyocyte (Dolle and Vijg, 2002). More recently, quantitative assays have been developed to comprehensively analyze genome structural variation by next-generation sequencing (Chiarle et al, 2011; Maslov et al, 2015; Quispe-Tintaya et al, 2016). Using these and other assays, which hopefully will emerge in the near future, it should be able to empirically confirm the impact of erroneous DSB repair on the aging process.…”

In vitro evaluation of the cyto-genotoxic potential of Ruthenium(II) SCAR complexes: a promising class of antituberculosis agents

“…The assessment that is required to be undertaken regarding the toxic effects of chemicals such as the candidates for new drugs, environmental and industrial compounds, among other agents, is an increasingly recurring challenge in our modern world. Contact with newly discovered molecules, even without knowledge of their biological activities, can cause harm to the human health in both short and long terms [20].…”

Micronucleus Based Genotoxicity Tests

“…These kind of mutations are more important because they may cause carcinogenesis, many kinds of congenital diseases and also aging. 3 So, genotoxicity assessment is an important process to keep human and animal health. Genotoxicity evaluation aims to identify the safety of many kinds of substances like food additives, pesticides, pharmaceuticals, chemicals used in cosmetics, veterinary drugs and living organisms like bacteria or virus.…”

“…Nevertheless, NGS methods about genotoxicity testing must be developed in application. 3 Three-dimensional skin models are also developing and one of the in vitro assay in the testing of applied cosmetic and pharmaceutical compounds. In this model, human keratinocyte in vitro culture is used.…”