Is a liver comparable to a liver? A comparison of different rat-derived S9-fractions with a biotechnological animal-free alternative in the Ames fluctuation assay

Brendt, Julia; Crawford, Sarah E.; Velki, Mirna; Xiao, Huang; Thalmann, Beat; Hollert, Henner; Schiwy, Andreas

doi:10.1016/j.scitotenv.2020.143522

Cited by 7 publications

(3 citation statements)

References 56 publications

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“…It has to be mentioned, that for the purpose of this study only two batches of S9 were compared and both were subjected to quality control by the supplier. Previous studies have found that significant variations between different types of S9 products are possible [ 44 , 45 ]. However, the present dataset indicates that Aroclor 1254-induced S9, which will not be available anymore in the near future, can likely be adequately replaced by PB/β-NF induced S9, without any anticipated negative impact on the LEC values.…”

Section: Discussionmentioning

confidence: 99%

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Direct Comparison of the Lowest Effect Concentrations of Mutagenic Reference Substances in Two Ames Test Formats

Rainer

Pinter

Prielinger

et al. 2021

Toxics

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The Ames assay is the standard assay for identifying DNA-reactive genotoxic substances. Multiple formats are available and the correct choice of an assay protocol is essential for achieving optimal performance, including fit for purpose detection limits and required screening capacity. In the present study, a comparison of those parameters between two commonly used formats, the standard pre-incubation Ames test and the liquid-based Ames MPF™, was performed. For that purpose, twenty-one substances with various modes of action were chosen and tested for their lowest effect concentrations (LEC) with both tests. In addition, two sources of rat liver homogenate S9 fraction, Aroclor 1254-induced and phenobarbital/β-naphthoflavone induced, were compared in the Ames MPF™. Overall, the standard pre-incubation Ames and the Ames MPF™ assay showed high concordance (>90%) for mutagenic vs. non-mutagenic compound classification. The LEC values of the Ames MPF™ format were lower for 17 of the 21 of the selected test substances. The S9 source had no impact on the test results. This leads to the conclusion that the liquid-based Ames MPF™ assay format provides screening advantages when low concentrations are relevant, such as in the testing of complex mixtures.

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Section: Discussionmentioning

confidence: 99%

“…In the long term an animal-free S9 source may become preferable [ 46 ]. While initial results looks highly promising [ 44 ], more data needs to be provided, before such material can be considered a valid alternative.…”

Section: Discussionmentioning

confidence: 99%

Direct Comparison of the Lowest Effect Concentrations of Mutagenic Reference Substances in Two Ames Test Formats

Rainer

Pinter

Prielinger

et al. 2021

Toxics

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“…This lack of homogeneity can generate variable genotoxic responses during in vitro assessments [6]. To overcome this problem, some alternatives have been proposed, such as the biotechnological animal free "ewoS9R" [7]. On the other hand, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline for the genotoxicity assessment of pharmaceuticals (ICH S2R1) recommends the use of alternative methods/systems for metabolic activation when negative results are obtained in vitro and further testing is considered [5].…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity of 12 Mycotoxins by the SOS/umu Test: Comparison of Liver and Kidney S9 Fraction

Alonso-Jauregui

González-Peñas

Cerain

et al. 2022

Toxins

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Liver S9 fraction is usually employed in mutagenicity/genotoxicity in vitro assays, but some genotoxic compounds may need another type of bioactivation. In the present work, an alternative S9 fraction from the kidneys was used for the genotoxicity assessment of 12 mycotoxins with the SOS/umu test. The results were compared with liver S9 fraction, and 2–4 independent experiments were performed with each mycotoxin. The expected results were obtained with positive controls (4-nitroquinoline-N-oxide and 2-aminoanthracene) without metabolic activation or with liver S9, but a potent dose-dependent effect with 4-nitroquinoline-N-oxide and no activity of 2-aminoanthracene with kidney S9 were noticed. Aflatoxin B1 was genotoxic with metabolic activation, the effect being greater with liver S9. Sterigmatocystin was clearly genotoxic with liver S9 but equivocal with kidney S9. Ochratoxin A, zearalenone and fumonisin B1 were negative in all conditions. Trichothecenes were negative, except for nivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, T-2 and HT-2 toxins, which showed equivocal results with kidney S9 because a clear dose-response effect was not observed. Most of the mycotoxins have been assessed with kidney S9 and the SOS/umu test for the first time here. The results with the positive controls and the mycotoxins confirm that the organ used for the S9 fraction preparation has an influence on the genotoxic activity of some compounds.

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Curcumol metabolized by rat liver S9 fraction and orally administered in mouse suppressed the proliferation of colon cancer in vitro and in vivo

Zhou

Moon

Kim

et al. 2023

Food Sci Biotechnol

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Is a liver comparable to a liver? A comparison of different rat-derived S9-fractions with a biotechnological animal-free alternative in the Ames fluctuation assay

Cited by 7 publications

References 56 publications

Direct Comparison of the Lowest Effect Concentrations of Mutagenic Reference Substances in Two Ames Test Formats

Direct Comparison of the Lowest Effect Concentrations of Mutagenic Reference Substances in Two Ames Test Formats

Genotoxicity of 12 Mycotoxins by the SOS/umu Test: Comparison of Liver and Kidney S9 Fraction

Curcumol metabolized by rat liver S9 fraction and orally administered in mouse suppressed the proliferation of colon cancer in vitro and in vivo

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