Strain-specific mutagenicity of NDMA and CPNP: insights from TA1535, TA100, and WP2 uvrA (pKM101) under metabolic activation

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2025-06-30 DOI:10.1016/j.etap.2025.104752

Chetan K. Kajavadara , Darshan T. Valani , Satyam N. Patel , Rushikesh M. Shukla , Laxit K. Bhatt , Rajesh J. Patel, Sunny P. Kumar, Rajesh Sundar, Mukul R. Jain

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Abstract

The Ames test is a critical assay for assessing the mutagenic potential of chemical compounds; however, its conventional version (OECD TG 471) falls short in detecting nitrosamine mutagenicity due to insufficient metabolic activation. Given the ubiquity of nitrosamines as environmental contaminants and drug impurities, an enhanced protocol incorporating 30 % v/v hamster and rat liver S9 fractions with a 30-minute pre-incubation is warranted. This study streamlined the enhanced Ames test by evaluating the sensitivity of S. typhimurium strains TA1535 and TA100, and E. coli WP2 uvrA (pKM101), against N‑nitrosodimethylamine (NDMA) and 1‑cyclopentyl‑4‑nitrosopiperazine (CPNP). Dose‑normalized fold‑induction metrics revealed that TA1535 offers superior sensitivity across varied S9 conditions. Hamster liver S9 generally enhanced mutagenic responses compared to rat liver S9. Notably, CPNP was more potent in TA1535 and TA100, while NDMA was more active in WP2 uvrA (pKM101) with rat S9. This optimized screening strategy minimizes resources and is recommended for initial nitrosamine impurity mutagenicity detection.

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NDMA和CPNP的菌株特异性诱变性：来自TA1535、TA100和WP2 uvrA （pKM101）代谢激活的见解

艾姆斯试验是评估化合物致突变潜力的关键试验；然而，其传统版本（OECD TG 471）由于代谢激活不足，在检测亚硝胺致突变性方面存在不足。鉴于亚硝胺作为环境污染物和药物杂质的普遍存在，有必要采用一种强化方案，将30 % v/v的仓鼠和大鼠肝脏S9组分与30分钟的预孵卵结合。本研究通过评价鼠伤寒沙门氏菌菌株TA1535和TA100以及大肠杆菌WP2 uvrA （pKM101）对N -亚硝基二甲胺（NDMA）和1 -环戊基- 4 -亚硝基哌嗪（CPNP）的敏感性，简化了增强的Ames试验。剂量归一化折叠诱导指标显示，TA1535在不同的S9条件下具有优越的灵敏度。与大鼠肝脏S9相比，仓鼠肝脏S9普遍增强了致突变反应。值得注意的是，CPNP在TA1535和TA100中更有效，而NDMA在大鼠S9的WP2 uvrA （pKM101）中更活跃。这种优化的筛选策略使资源最小化，并推荐用于亚硝胺杂质致突变性的初始检测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.