Bhas 42 Cell Transformation Assay for Genotoxic and Non-Genotoxic Carcinogens

Sasaki, Kiyoshi; Huk, Anna; Yamani, Naouale El; Tanaka, Noriho; Dušinská, Maria

doi:10.1007/978-1-4939-1068-7_20

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…Therefore, for a complete picture of genotoxicity, we need to perform assays covering other relevant endpoints, such as gene mutation, structural chromosomal damage and aneuploidy which are indicative of genotoxic carcinogens. Cell transformation assays can give additional valuable information about genotoxic and non-genotoxic carcinogens (19).…”

Section: Discussionmentioning

confidence: 99%

In vitrogenotoxicity testing of four reference metal nanomaterials, titanium dioxide, zinc oxide, cerium oxide and silver: towards reliable hazard assessment

Yamani

Collins

Rundén-Pran

et al. 2016

MUTAGE

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100

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There is serious concern about the potential harmful effects of certain nanomaterials (NMs), on account of their ability to penetrate cell membranes and the increased reactivity that results from their increased surface area compared with bulk chemicals. To assess the safety of NMs, reliable tests are needed. We have investigated the possible genotoxicity of four representative NMs, derived from titanium dioxide, zinc oxide, cerium oxide and silver, in two human cell lines, A549 alveolar epithelial cells and lymphoblastoid TK6 cells. A high-throughput version of the comet assay was used to measure DNA strand beaks (SBs) as well as oxidised purines (converted to breaks with the enzyme formamidopyrimidine DNA glycosylase). In parallel, cytotoxicity was measured with the alamarBlue® assay, and the ability of NM-treated cells to survive was assessed by their colony-forming efficiency. TiO and CeO NMs were only slightly cytotoxic by the alamarBlue® test, and had no long-term effect on colony-forming efficiency. However, both induced DNA damage at non-cytotoxic concentrations; the damage decreased from 3 to 24-h exposure, except in the case of CeO-treated A549 cells. ZnO and Ag NMs affected cell survival, and induced high levels of DNA damage at cytotoxic concentrations. At lower concentrations, there was significant damage, which tended to persist over 24 h. The implication is that all four reference metal NMs tested-whether cytotoxic or not-are genotoxic. A full assessment of NM toxicity should include tests on different cell types, different times of incubation and a wide range of (especially non-cytotoxic) concentrations; a test for cell viability should be performed in parallel. Inclusion of Fpg in the comet assay allows detection of indirect genotoxic effects via oxidative stress.

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Section: Discussionmentioning

confidence: 99%

In vitrogenotoxicity testing of four reference metal nanomaterials, titanium dioxide, zinc oxide, cerium oxide and silver: towards reliable hazard assessment

Yamani

Collins

Rundén-Pran

et al. 2016

MUTAGE

Self Cite

100

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“…This also facilitates identifying the genotoxic carcinogens apart from nongenotoxic NMs ( Steinberg, 2016 ). Endpoints for the safe NPs include unchanged morphology, with retained density-dependent growth and colonies formation, devoid of any crisscrossed cell or Piled-up cell foci, etc., ( Sasaki et al, 2014 ). In 2015, the European Union Reference Laboratory for Animal Test alternatives also published a paper to test chemicals for carcinogenicity using an In Vitro Syrian Hamster Embryocell Transformation Assay ( Drasler et al, 2017 ; Dickinson et al, 2019 ).…”

Section: Novel Methods Employed For Nanotoxicity Evaluationmentioning

confidence: 99%

Novel Methods and Approaches for Safety Evaluation of Nanoparticle Formulations: A Focus Towards In Vitro Models and Adverse Outcome Pathways

et al. 2021

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Nanotoxicology is an emerging field employed in the assessment of unintentional hazardous effects produced by nanoparticles (NPs) impacting human health and the environment. The nanotoxicity affects the range between induction of cellular stress and cytotoxicity. The reasons so far reported for these toxicological effects are due to their variable sizes with high surface areas, shape, charge, and physicochemical properties, which upon interaction with the biological components may influence their functioning and result in adverse outcomes (AO). Thus, understanding the risk produced by these materials now is an important safety concern for the development of nanotechnology and nanomedicine. Since the time nanotoxicology has evolved, the methods employed have been majorly relied on in vitro cell-based evaluations, while these simple methods may not predict the complexity involved in preclinical and clinical conditions concerning pharmacokinetics, organ toxicity, and toxicities evidenced through multiple cellular levels. The safety profiles of nanoscale nanomaterials and nanoformulations in the delivery of drugs and therapeutic applications are of considerable concern. In addition, the safety assessment for new nanomedicine formulas lacks regulatory standards. Though the in vivo studies are greatly needed, the end parameters used for risk assessment are not predicting the possible toxic effects produced by various nanoformulations. On the other side, due to increased restrictions on animal usage and demand for the need for high-throughput assays, there is a need for developing and exploring novel methods to evaluate NPs safety concerns. The progress made in molecular biology and the availability of several modern techniques may offer novel and innovative methods to evaluate the toxicological behavior of different NPs by using single cells, cell population, and whole organisms. This review highlights the recent novel methods developed for the evaluation of the safety impacts of NPs and attempts to solve the problems that come with risk assessment. The relevance of investigating adverse outcome pathways (AOPs) in nanotoxicology has been stressed in particular.

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“…This assay was carried out by adapting the in vitro Bhas 42 cell transformation assay method described in the OECD Guidance Document No. 231 (2017) based on the work of Sasaki et al (2014).…”

Section: Carcinogenesismentioning

confidence: 99%

A continuous in silico learning strategy to identify safety liabilities in compounds used in the leather and textile industry

March-Vila

Ferretti²,

Terricabras³

et al. 2023

Arch Toxicol

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There is a widely recognized need to reduce human activity's impact on the environment. Many industries of the leather and textile sector (LTI), being aware of producing a significant amount of residues (Keßler et al. 2021; Liu et al. 2021), are adopting measures to reduce the impact of their processes on the environment, starting with a more comprehensive characterization of the chemical risk associated with the substances commonly used in LTI. The present work contributes to these efforts by compiling and toxicologically annotating the substances used in LTI, supporting a continuous learning strategy for characterizing their chemical safety. This strategy combines data collection from public sources, experimental methods and in silico predictions for characterizing four different endpoints: CMR, ED, PBT, and vPvB. We present the results of a prospective validation exercise in which we confirm that in silico methods can produce reasonably good hazard estimations and fill knowledge gaps in the LTI chemical space. The proposed protocol can speed the process and optimize the use of resources including the lives of experimental animals, contributing to identifying potentially harmful substances and their possible replacement by safer alternatives, thus reducing the environmental footprint and impact on human health.

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Bhas 42 Cell Transformation Assay for Genotoxic and Non-Genotoxic Carcinogens

Cited by 8 publications

References 35 publications

In vitrogenotoxicity testing of four reference metal nanomaterials, titanium dioxide, zinc oxide, cerium oxide and silver: towards reliable hazard assessment

In vitrogenotoxicity testing of four reference metal nanomaterials, titanium dioxide, zinc oxide, cerium oxide and silver: towards reliable hazard assessment

Novel Methods and Approaches for Safety Evaluation of Nanoparticle Formulations: A Focus Towards In Vitro Models and Adverse Outcome Pathways

A continuous in silico learning strategy to identify safety liabilities in compounds used in the leather and textile industry

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