[Modification of esophageal epithelium DNA in the human fetus by N-nitrosomethylbenzylamine (NMBzA)].
Human fetal esophageal epithelium, after being exposed to NMBzA, was found to contain O6-methyldeoxyguanine (O6-MedG), a NMBzA-modified DNA adduct, in tissue DNA by radioimmunoassay and monoclonal antibody, which is highly specific to O6-MedG. The highest level of O6-MedG was 58.83 pMol/mg DNA after adding 5.0 mM NMBzA in vitro. The level of O6-MedG and the concentration of NMBzA followed the dose-effect relationship. O6-MedG could be eliminated from DNA by normal human fetal esophageal epithelium. About 50% of O6-MedG was cleared away in the first 1-2 hours during the post-treatment incubation, which was followed by a slower phase of elimination with 18% left in 24 hours. The results indicate that the human fetal esophageal epithelium can metabolically activate NMBzA in vitro and form O6-MedG, which, as well known, can cause mutagenesis and carcinogenesis and, hence, may most likely be related to the development of human esophageal cancer.
Feng
L
L
Cancer Institute, Chinese Academy of Medical Sciences, Beijing.
Lu
S X
SX
D002273:Carcinogens / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism*; D005333:Fetus; D006801:Humans
D002273:Carcinogens; D004247:DNA; C014707:nitrosobenzylmethylamine; C015558:O(6)-methyl-2'-deoxyguanosine; D003849:Deoxyguanosine; D004128:Dimethylnitrosamine