Sterigmatocystin (ST), being a precursor of aflatoxin, is categorized as Group 2B carcinogen. Our previous studies found that both mismatch repair (MMR) pathways and p53 signaling pathway were involved in ST-induced G₂ cell cycle arrest in human esophageal squamous epithelial cell line, HET-1A, in vitro. Studies showed that ERK, JNK and p38 signaling pathways played important roles in cell cycle arrest induced by several other carcinogens. However, the role of MAPK pathway and the links between the MMR and p53 signaling pathways in ST induced G₂ phase arrest is still not clarified. In the present study, we first explored the role of MAPK pathway upon ST induced G₂ arrest, and found that ST up-regulated the expression of G₂/M regulatory factors through MAPK signaling pathway (both ERK and p38, but not JNK pathway). The inhibition of ERK and p38 significantly inhibited p53 activation by ST. Blockage of MMR pathway by silencing hMLH1 expression inhibited ERK, p38 and p53 activation and then attenuated G₂ arrest by ST. Thus, in conclusion, the current study demonstrated that in response to ST induced DNA damage, hMLH1 was first activated, then triggered ERK, p38 and p53 activation and finally resulted in G₂ arrest in HET-1A cells.

曲霉毒素（ST）是黄曲霉毒素的前体，被归类为2B类致癌物。我们先前的研究发现，错配修复（MMR）途径和p53信号传导途径均与ST诱导的人食管鳞状上皮细胞系HET-1A在体外的G ₂细胞周期阻滞有关。研究表明，ERK，JNK和p38信号通路在其他几种致癌物诱导的细胞周期停滞中起着重要作用。然而，尚不清楚MAPK通路的作用以及MMR和p53信号通路之间的联系在ST诱导的G ₂期阻滞中的作用。在本研究中，我们首先探讨了MAPK途径在ST诱导G ₂阻滞中的作用，并发现ST上调了G的表达₂ / M调节因子通过MAPK信号通路（ERK和p38均起作用，但JNK通路不起作用）。ERK和p38的抑制作用显着抑制ST激活p53。通过沉默hMLH1表达来阻断MMR通路可抑制ERK，p38和p53活化，然后减弱ST阻滞G ₂。因此，总而言之，当前的研究表明，响应于ST诱导的DNA损伤，hMLH1首先被激活，然后触发ERK，p38和p53激活，最后导致G ₂停滞在HET-1A细胞中。