柑橘素 (CIT) 是一种由青霉属、曲霉属和红曲霉属产生的聚酮化合物霉菌毒素，是一种在各种食品中发现的污染物，也在室内灰尘中检测到。多项研究表明，CIT 可能损害动物的肾脏、肝脏、心脏、免疫和生殖系统，其机制迄今尚未完全阐明。在这项研究中，我们研究了 CIT 对两种人类肿瘤细胞系 HepG2（肝细胞癌）和 A549（肺腺癌）的作用模式。使用MTT增殖测定法测定细胞毒性浓度。使用碱性彗星测定研究亚 IC50 浓度的基因毒性作用，并使用流式细胞术研究对细胞周期的影响。此外，通过基于细胞的 ELISA 确定了 CIT 对两种细胞周期检查点蛋白（丝氨酸/苏氨酸激酶 Chk2 和范可尼贫血 (FA) D2 组 (FANCD2)）总量和磷酸化的影响。使用GraphPad Prism统计软件分析数据。 HepG2 的 CIT IC50 为 107.3 µM，A549 的 CIT IC50 >250 µM。结果表明，对 CIT 的敏感性具有细胞类型依赖性，亚 IC50 和接近 IC50 的 CIT 会诱导显着的 DNA 损伤和细胞周期停滞在 G2/M 期，这与总 Chk2 和磷酸化 Chk2 和磷酸化 Chk2 的增加有关。 HepG2 和 A549 细胞中的 FANCD2 检查点蛋白。

Citrinin (CIT), a polyketide mycotoxin produced by Penicillium, Aspergillus, and Monascus species, is a contaminant that has been found in various food commodities and was also detected in house dust. Several studies showed that CIT can impair the kidney, liver, heart, immune, and reproductive systems in animals by mechanisms so far not completely elucidated. In this study, we investigated the CIT mode of action on two human tumor cell lines, HepG2 (hepatocellular carcinoma) and A549 (lung adenocarcinoma). Cytotoxic concentrations were determined using an MTT proliferation assay. The genotoxic effect of sub-IC50 concentrations was investigated using the alkaline comet assay and the impact on the cell cycle using flow cytometry. Additionally, the CIT effect on the total amount and phosphorylation of two cell-cycle-checkpoint proteins, the serine/threonine kinase Chk2 and Fanconi anemia (FA) group D2 (FANCD2), was determined by the cell-based ELISA. The data were analyzed using GraphPad Prism statistical software. The CIT IC50 for HepG2 was 107.3 µM, and for A549, it was >250 µM. The results showed that sensitivity to CIT is cell-type dependent and that CIT in sub-IC50 and near IC50 induces significant DNA damage and cell-cycle arrest in the G2/M phase, which is related to the increase in total and phosphorylated Chk2 and FANCD2 checkpoint proteins in HepG2 and A549 cells.