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本文报道食管癌高发区粮食中优势污染菌互隔交链孢霉代谢产物交链孢酚(AOH)对人胎儿食管上皮组织癌基因的激活。结果表明,体外培养的人胎儿食管上皮组织经10gg/ml AOH作用4h后,其DNA具有转化活性,可转化NIH/3T3细胞。一轮转化率为0.17Foci/μg DNA,二轮转化率为0.58Foci/μg DNA(P<0.01)。转化细胞中含有人特异性高重复序列Alu,提示转化系人DNA转染所致。Southern blot检测表明,AOH处理后的人胎儿食管上皮组织内有H-ras和myc基因的扩增,经其转染的NIH/3T3细胞中亦有H-ras基因持久而稳定的扩增。对照组胎儿食管上皮和正常NIH/3T3细胞中均未发现相应的同源序列,说明正常胎儿食管组织中的H-ras和myc基因可经AOH短期处理而激活。该结果对AOH可能系人食管癌病因之一提供了直接证据。
This article reports the activation of the oncogene in human fetal esophageal epithelial tissue by the inoculation of the Alternaria alternata Alternoxin (AOH), a predominant contaminant in grain, in esophageal cancer-prone areas. The results showed that the DNA of human fetal esophageal epithelial cells cultured in vitro with 10gg / ml AOH for 4h could transform the NIH / 3T3 cells. One round of conversion was 0.17 Foci / μg DNA and the second round of conversion was 0.58 Foci / μg DNA (P <0.01). Transformed cells contain human-specific high repetitive sequence Alu, suggesting that transfection of human DNA transfection. Southern blot analysis showed that H-ras gene and myc gene were amplified in AOH-treated human fetal esophageal epithelial cells, and H-ras gene was also amplified stably and stably in NIH / 3T3 cells transfected with AOH. The corresponding homologous sequences were not found in the control group of fetal esophageal epithelium and normal NIH / 3T3 cells, indicating that H-ras and myc genes in normal fetal esophageal tissue can be activated by AOH short-term treatment. This result provides direct evidence that AOH may be one of the causative agents of human esophageal cancer.