Evidence map›Paper›PMID 42018426›Full record

ArticleEnvironmental and molecular mutagenesis2026

Adjusting the Preincubation Conditions to Enhance the Ames Test for Detecting the Mutagenicity of N-Nitrosamines.

Michelle E Bishop, Audrey M Sims, Sharon K Guerrero, Kamela Mitchell, Nan Mei, Hannah Xu, Naomi L Kruhlak, Sruthi T King, Robert T Dorsam, Aisar H Atrakchi and 2 more

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In one paragraph

Article in Environmental and molecular mutagenesis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Michelle E BishopUS Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, USA.
Audrey M SimsUS Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, USA.
Sharon K GuerreroUS Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, USA.
Kamela MitchellUS Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, USA.
Nan MeiUS Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, USA.ORCID 0000-0002-3501-9014
Hannah XuUS Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, USA.
Naomi L KruhlakU.S Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA.
Sruthi T KingU.S Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA.
Robert T DorsamU.S Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA.
Aisar H AtrakchiU.S Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA.
Timothy J McGovernU.S Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA.
Robert H HeflichUS Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, USA.

Funding

CDER Office of Pharmaceutical QualityFDA/CDER Director's OfficeFDA/NCTR, Jefferson, AR 72079 USARegulatory Science Research grant from the FDA/CDER Office of New Drugs
6 · The paper itself

Abstract

Conducting S9-mediated preincubations at slightly acid pHs (e.g., pH 5.0 to pH 6.5) has been reported to enhance the mutagenicity of small-molecule nitrosamines in the Ames test. In this study, we have evaluated the effect of adjusting the preincubation mix used in the Enhanced Ames Test (EAT) from pH 7.4 to pH 6.0 and supplying the activation mix with preformed reducing equivalents (NADPH and NADH). Abbreviated EAT assays were conducted on five small-molecule N-nitrosamines and 10 nitrosamine drug substance-related impurities (NDSRIs) with tester strains TA1535 and WP2 uvrA (pKM101) and using S9 mixes containing 30% hamster liver S9. Testing on small-molecule nitrosamines found that the pH 6.0 preincubation mix enhanced the mutagenicity of N-nitroso-dimethylamine and N-nitroso-diethylamine but not N-nitroso-diphenylamine, N-nitroso-methyl-4-aminobutyric acid or N-(2,2-diethoxyethyl)-2,2-diethoxy-N-nitrosoethanamine. Of the 10 NDSRIs that were tested, N-nitroso-phenylephrine was consistently positive with the pH 6.0 preincubation mix, while it was generally negative with pH 7.4 preincubation mixes. The mutagenicity of the nine other NDSRIs that were tested was not changed by the slightly acid preincubation mix. The results indicate that performing preincubation reactions under slightly acid conditions increases the mutagenicity of some small-molecule nitrosamines, and in one case, produced a positive mutagenic response with an NDSRI that was otherwise negative in the EAT.

Indexed as

MutagensNitrosaminesAnimalsCricetinaeHydrogen-Ion ConcentrationMutagenicity TestsSalmonella typhimuriumMutagensNitrosaminesdrug impurityenhanced Ames testEscherichia coli WP2 uvrA (pKM101)hamster liver S9preincubationSalmonella typhimurium TA1535

Identifiers

PMID42018426
PMCPMC13102042

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