[Studies on the activation of oncogenes by alternariol monomethyl ether in human fetal esophageal epithelium].

Activation of oncogenes in human fetal esophageal epithelium by alternariol monomethyl ether (AME) is reported. AME is a main metabolite of Alternaria alternata which is considered to be a dominant pollutant in the harvested grain in Linxian County (a high risk area of esophageal cancer). It was found that NIH/3T3 cells were transformed via transfection of DNA extracted from human fetal esophageal epithelium having been treated with AME in short term in vitro. The transformed cells formed clony when inoculated in 0.3% soft agar, and developed solid tumor after inoculated subcutaneously into BALB/C nude mice. Molecular hybridization experiment proved in the genome of transformed cells that there were sequences which hybridized with Alu probe. When hybridized with oncogene probes by means of Southern hybridization, samples of human fetal esophageal epithelium treated with AME showed marked amplification of c-H-ras and c-myc genes; DNA from transformed NIH/3T3 cells via transfection of genes of tissues mentioned above showed also significant amplification of c-H-ras gene. It demonstrated that c-H-ras and c-myc oncogenes in normal human fetal esophagus could be activated by a short-term treatment of AME in vitro. These results are considered to be the direct evidence of the view that AME may be one of the etiologic factors of human esophageal cancer.