交链孢酚激活人胎食管上皮组织细胞癌基因的研究

Studies on the activation of oncogenes by alternariol in human fetal esophageal epithelium

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 paper reported that the activation of oncogenes in human fetal esopha geal epithelium treated by alternariol (AOH). It was found that NIH/3T3 cells were transformed via transfeetion of DNA extracted from human fetal esophageal epithelium which was cultured and treated by 10μg/ml AOH in a short term in vitro. The efficiency of primary loci was 0.17 focus per μg of DNA. In the secondary transfection, the efficiency was 0.58 focus per μg of DNA (P<0.01). The Alu sequences, which are specific for human, were found in the genome of transformed cells. This indicated that the malignant transformation of NIH/3T3 cells was induced by human DNA transfection. The results of Sourthern hybridization indicated that the samples of human fetal esophageal epithelium treated with 10μg/ml of AOH showed obvious amplification of C-H-ras and C-myc genes. The DNA from transformed NIH/3T3 cells also showed significant amplification of C-H-ras gene. On the contrary,, the samples from untreated human fetal esophageal epithelium and normal NIH/3T3 cells showed no amplification of those oncogenes. These results provide a direct evidence for the suggestion that AOH may be a causative agent of human esophageal csncer.