树叶,茎,和Annonaatemya的果实(A.atemoya;AA),番荔枝科的一种水果植物,表现出抗血管生成,抗氧化,抗炎,和神经保护活动。然而,AA的安全性尚未得到全面阐明。在这项研究中,我们使用构成体外哺乳动物染色体畸变的标准三测试电池评估了AA叶(AAL)乙醇提取物的潜在遗传毒性,体内微核,和细菌反向突变(也称为Ames测试)测试,根据韩国食品和药品安全部的建议。体外染色体畸变分析显示AAL提取物不诱导结构或数值畸变,有或没有代谢激活(S9)。体内微核分析显示,AAL提取物处理后,微核多色红细胞(PCE)的数量和PCE/正常染色红细胞的比率与阴性对照没有实质性差异。未观察到体重和死亡率的变化。然而,AAL提取物部分诱导诱变活性在所有三个细菌菌株在细菌回复突变试验,这表明它可能有助于确定AAL的基因毒性安全性。使用TK6细胞进行QuantSeq3\'mRNA测序分析以阐明AAL提取物的遗传毒性机制,揭示AAL的遗传毒性作用可能与细胞形态相关(细胞发育和角质化)有关,核苷酸代谢,和电子传输链功能。
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The leaves, stems, and fruits of Annona atemoya (A. atemoya; AA), a fruit-bearing plant of the family Annonaceae, exhibit anti-angiogenic, anti-oxidative, anti-inflammatory, and neuroprotective activities. However, the safety of AA has not been comprehensively elucidated. In this study, we evaluated the potential genotoxicity of an AA leaf (AAL) ethanol extract using a standard three-test battery constituting in vitro mammalian chromosomal aberration, in vivo micronucleus, and bacterial reverse mutation (also known as the Ames test) tests, as recommended by the Ministry of Food and Drug Safety of Korea. In vitro chromosomal aberration assay revealed that AAL extract did not induce structural or numerical aberrations, with or without metabolic activation (S9). In vivo micronucleus assay revealed that the number of micronucleated polychromatic erythrocytes (PCEs) and the PCE/normochromatic erythrocyte ratio after AAL extract treatment were not substantially different from those in the negative control. Changes in body weight and mortality were not observed. However, AAL extract partially induced mutagenic activity in all three bacterial strains in the bacterial reverse mutation assay, indicating that it could potentially aid in determining the genotoxic safety of AAL. QuantSeq 3\' mRNA sequencing analysis to elucidate the genotoxicity mechanisms of AAL extract using TK6 cells revealed that the genotoxic effects of AAL may be associated with cellular morphology-associated (cell development and keratinization), nucleotide metabolism, and electron transport chain functions.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s43188-024-00241-4.