[Alterations of oncogenes in human fetal esophageal epithelium induced by N-methylbenzylnitrosamine (NMBzA)].
Epidemiological investigation showed that N-methylbenzylnitrosamine (NMBzA) has been associated with increased incidence of esophageal cancer (EC) in Linxian county, a high incidence area. In present study, our results indicate that NMBzA can induce amplification and over-expression of EGFr gene in human fetal esophageal epithelium (HFE) treated with NMBzA for 24 hours as shown by southern blot assay and immunohistochemistry. The papillary hyperplasia was induced in HFEs that cultured with NMBzA for 1 to 3 weeks. Amplification of c-myc and int-2 gene in HFEs treated by NMBzA for 1 week and 3 weeks was found, respectively. Deletions of p53 and Rb gene were found in human fetal esophageal carcinomas induced by NMBzA. Overexpression of p53 protein in human fetal esophageal carcinomas detected by immunohistochemical methods indicates that p53 gene mutation(s) may be occured. The HFE explants treated in vitro with NMBzA for 3 weeks were inoculated subcutanously into balb/c nude mice. No tumor was found in 5 months after inoculation, suggesting that only changes of oncogene(s) are insufficient to induce full transformation. Other genetic alterations (such as functional inactivation of Rb or/and p53 tumor suppressor genes) may be necessary in the further progression of malignant lesions.
Guo
Y J
YJ
Cancer Institute, Chinese Academy of Medical Sciences Peking Union of Medical College, Beijing.
Lu
S X
SX
Liang
Y Y
YY
D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics*; D046508:Culture Techniques; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives; D004848:Epithelium / Q000473:pathology; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000235:genetics*; D004947:Esophagus; D005333:Fetus; D005784:Gene Amplification; D017353:Gene Deletion; D016161:Genes, Retinoblastoma; D018773:Genes, erbB-1; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D006965:Hyperplasia; D011519:Proto-Oncogenes
D002273:Carcinogens; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine