Shukla Rushikesh M, Valani Darshan T, Kajavadara Chetan K, Patel Satyam N, Patel Rajesh J, Bhatt Laxit K, Sundar Rajesh, Jain Mukul R
Department of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, India.
Environ Mol Mutagen. 2025 Jun;66(5):291-297. doi: 10.1002/em.70018. Epub 2025 Jun 8.
The Ames test is a fundamental assay for evaluating chemical mutagenicity, particularly for nitrosamines, which are widespread environmental and pharmaceutical contaminants. To improve sensitivity, regulatory agencies have endorsed the enhanced Ames test (EAT), which incorporates five tester strains, a 30-min pre-incubation step, and metabolic activation using both rat and hamster liver S9 fractions. While Salmonella typhimurium TA102 is known for its sensitivity to oxidative mutagens, its performance under EAT conditions has not been fully characterized. This study evaluated the mutagenic response of TA102 using two nitrosamine positive controls: N-nitrosodimethylamine (NDMA) and 1-cyclopentyl-4-nitrosopiperazine (CPNP). E. coli WP2 uvrA(pKM101) showed consistent mutagenic responses to both NDMA and CPNP, consistent with existing EAT data. TA102 demonstrated a robust response to NDMA but not to CPNP, suggesting limited sensitivity to certain nitrosamines. These findings support the continued use of WP2 uvrA(pKM101) in EAT protocols and highlight the limited utility of TA102 for comprehensive nitrosamine mutagenicity assessment.
艾姆斯试验是评估化学物质致突变性的一项基本检测方法,尤其适用于亚硝胺,亚硝胺是广泛存在的环境污染物和药物污染物。为提高检测灵敏度,监管机构认可了增强型艾姆斯试验(EAT),该试验采用五种测试菌株、30分钟预孵育步骤,并使用大鼠和仓鼠肝脏S9组分进行代谢活化。虽然鼠伤寒沙门氏菌TA102以对氧化诱变剂敏感而闻名,但其在EAT条件下的表现尚未得到充分表征。本研究使用两种亚硝胺阳性对照物N-亚硝基二甲胺(NDMA)和1-环戊基-4-亚硝基哌嗪(CPNP)评估了TA102的诱变反应。大肠杆菌WP2 uvrA(pKM101)对NDMA和CPNP均表现出一致的诱变反应,与现有的EAT数据一致。TA102对NDMA表现出强烈反应,但对CPNP没有反应,这表明其对某些亚硝胺的敏感性有限。这些发现支持在EAT方案中继续使用WP2 uvrA(pKM101),并突出了TA102在全面评估亚硝胺致突变性方面的有限效用。