West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, Sichuan, China.
Mycotoxin Res. 2022 Nov;38(4):231-241. doi: 10.1007/s12550-022-00466-y. Epub 2022 Aug 1.
Alternariol (AOH) is one of the toxins of Alternaria, and it has been widely detected in a variety of foods. It has been reported to be cytotoxic, dermally toxic, genotoxic, and potentially carcinogenic in vitro. However, in vivo toxicity data are lacking. This study used a novel in vivo 28-day multi-endpoint (Pig-a assay + micronucleus test + comet assay) genotoxicity evaluation system to evaluate the general toxicity and genotoxicity of AOH. A total of 42 male Sprague-Dawley rats were randomly distributed into three AOH-treated groups (5.51, 10.03, and 22.05 µg/kg bw), one AOH high-dose recovery group (AOH-HR, 22.05 µg/kg bw), one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw), and two vehicle control groups (corn oil and PBS). Treatments were administered by oral gavage for 28 consecutive days. Histopathological lesions were observed in the liver, kidney, and spleen in all AOH-treated groups. No statistical difference was found in each genotoxicity index within 28 days in the AOH-treated groups compared with those in the corn oil group. On day 42, in the AOH-HR group, the rate of Pig-a mutant phenotype reticulocytes (RET) significantly increased. On day 56, both RET and the rate of Pig-a mutant phenotype erythrocytes (RBC) were significantly reduced. These findings indicated that AOH might cumulatively induce genetic mutations.
交链孢酚（AOH）是交链孢霉的一种毒素，广泛存在于各种食物中。已有报道称，AOH 在体外具有细胞毒性、皮肤毒性、遗传毒性和潜在致癌性。然而，体内毒性数据尚缺乏。本研究采用新型体内 28 天多终点（Pig-a 试验+微核试验+彗星试验）遗传毒性评价系统，评估 AOH 的一般毒性和遗传毒性。共 42 只雄性 Sprague-Dawley 大鼠随机分为三组 AOH 处理组（5.51、10.03 和 22.05μg/kg bw）、一个 AOH 高剂量恢复组（AOH-HR，22.05μg/kg bw）、一个阳性对照组（N-乙基-N-亚硝脲，40mg/kg bw）和两个溶剂对照组（玉米油和 PBS）。连续 28 天通过灌胃给予处理。在所有 AOH 处理组中均观察到肝脏、肾脏和脾脏的组织病理学损伤。在 AOH 处理组中，各遗传毒性指标在 28 天内与玉米油组相比均无统计学差异。在 AOH-HR 组中，第 42 天，Pig-a 突变表型网织红细胞（RET）的比率显著增加。在第 56 天，RET 和 Pig-a 突变表型红细胞（RBC）的比率均显著降低。这些发现表明，AOH 可能会累积诱导遗传突变。
