Search

Abstract: Aflatoxins (AF) are the mycotoxin with the carcinogenic effect produced by the fungi like Aspergillus flavus, including AFB1, B2, G1, G2, M1, and so on. The detection rate of Aflatoxin G1 (AFG1) is very high in the diet of residents in the high incidence area of the gastric carcinoma and esophageal carcinoma in China, which is the main polluting mycotoxin of the local grain. However, there were no available data regarding the gastric toxicity of AFG1 up to now. In the present study, The toxicity of AFG1 in vitro-cultured human primary adult esophageal epithelial cells was explored by employing the methods of Western blot, semi-quantitative RT-PCR and observing the effect of AFG1 on the expression of the HLA-I molecules of the human esophageal epithelial cells and the antigen processing relative genes TAP-1 and LMP-2. The results showed that AFG1 treatment could decrease both the protein expression of HLA-ABC of the cell surface and the mRNA expression of HLA-A and HLA-B. Moreover, In the AFG1 treatment groups of different densities, both the TAP-1 mRNA and protein expression level of the human esophageal epithelial cells decreased. Furthermore, the LMP-2 protein expression level of the human esophageal epithelial cells decreased, while the mRNA expression level was not obviously changed by AFG1 treatment. It is indicated that the decrease of the HLA-I expression of the cell surface was probably dependent on the decrease of the TAP-1 and LMP-2 expression to a great extent. The decrease of LMP-2 expression resulted in the decrease of HLA-I expression and stability in the cell membrane and finally led to the defect in the antigen presentation, which hindered its identification by the T lymphocytes, made it escape the immune surveillance, and then caused the tumor genesis. [Copyright &y& Elsevier]

Abstract: Sterigmatocystin (ST), a common environmental contaminant found across the world, is generally recognized as a potential carcinogen, mutagen and teratogen. Our previous epidemiological studies suggested that ST exposure might be a risk factor for esophageal cancer. However, the direct effects of ST on human esophageal epithelial cells are currently unknown. In the present study, we examined the effect of treating a human esophageal epithelial cell line (Het-1A) with ST on DNA damage, DNA repair mechanisms, and cell cycle distribution. We found that ST treatment could induce DNA damage and lead to a G2 phase arrest, associated with a marked up-regulation of G2/M regulatory proteins, including Cyclin B1, Cdc2/p-Cdc2, and Cdc25C/p-Cdc25C. Additionally, we found that the expression of two mismatch repair (MMR) proteins, hMLH1 and hMSH2, was up-regulated at both the mRNA and protein levels after ST treatment, suggesting that ST could induce the MMR system in Het-1A cells. Interestingly, ST-induced G2 phase arrest was mediated by hMLH1 up-regulation, but was independent of hMSH2. Treatment with hMLH1-siRNA prevented the up-regulation of Cyclin B1, Cdc2/p-Cdc2 and Cdc25C/p-Cdc25C in ST-treated cells, thereby inhibiting the subsequent G2 phase arrest of Het-1A cells. Moreover, we found that hMLH1 may act as a direct sensor of ST-mediated DNA damage. In conclusion, the study demonstrated that ST caused DNA damage and triggered G2 phase arrest in Het-1A cells, and hMLH1 participated in the ST-induced G2 phase arrest by up-regulating G2/M regulatory proteins. [Copyright &y& Elsevier]

Abstract: Ochratoxin A (OTA) is a mycotoxin commonly found in several food commodities worldwide. OTA exposure was involved in the nephrotoxicity, hepatotoxicity as well as immunotoxicity in experimental model. Our previous study showed that the high level of OTA contamination in wheat might be related to the high incidence of gastric carcinoma in rural area of China. However, there were no available data regarding the gastric toxicity of OTA up to now. In the present study, we explored the toxicity of OTA in human gastric epithelium immortalized cells (GES-1) by analyzing the regulation of the cell cycle, apoptosis and its molecular mechanism. We found that OTA could induce GES-1 cells arrested in G2/M phase. Among these cycle-arrested cells, the proportion of cells in M phase was down-regulated after OTA treatment by the mitotic index and the level of phospho-histone H3. Thus, it was clear that OTA exerted a major influence on G2 phase arrest instead of M phase. We further detected the expression of the key factors which are critical to the G2/M phase transmission such as Cdc25C, Cdc2 and cyclinB1. The cyclinB1–Cdc2 complex was reduced and the expression of Cdc25C, Cdc2 and cyclinB1 were significantly decreased by OTA treatment both at protein and mRNA level, respectively. Considering that the cells may undergo apoptosis or death due to the cell cycle arrest, so we next detected the apoptosis of cells by OTA treatment. The results confirmed that OTA did induce apoptosis of GES-1 cells and activate the cleavage of capase-3. In conclusion, cell apoptosis and G2 phase arrest mediated by Cdc25C, Cdc2 and cyclinB1 may be the initiating event in the gastric toxicity of OTA. [Copyright &y& Elsevier]