Normal human bronchial epithelial cells do not show an adaptive response after treatment with N-methyl-N'-nitro-N-nitrosoguanidine.
Normal human bronchial epithelial cells cultured in serum-free medium were exposed to low doses o N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to examine whether increased cellular resistance and increased activity of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase could be induced. After treatment with single doses of MNNG a dose-dependent decrease in O6-methylguanine-DNA methyltransferase activity was observed, as expected for this unique repair system. The activity recovered to the starting level in about 24 h when a dose that consumed approximately 65% of the enzyme activity (0.2 micrograms/ml) was given, but did not exceed the activity in the untreated control. Furthermore, treatment every 6 h for 4-5 days with non-toxic concentrations of MNNG (0.04-0.12 micrograms/ml) did not increase O6-methylguanine-DNA methyltransferase activity. Neither was cell survival following a range of challenge doses significantly increased. Our data suggest that human bronchial epithelial cells do not adapt to MNNG.
D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D008780:Methyltransferases / Q000096:biosynthesis* / Q000502:physiology; D019853:O(6)-Methylguanine-DNA Methyltransferase
D008769:Methylnitronitrosoguanidine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase