Chemical carcinogen-induced damage to the c-neu and c-myc protooncogenes in rat lung epithelial cells: possible mechanisms for differential repair in transcriptionally active genes.
N-methyl-N'-nitro-N-nitrosoguanidine (M-NNG)-induced damage to two transcriptionally active genes, c-neu and c-myc, was studied in rat lung epithelial cells in vitro. MNNG, a direct acting alkylating agent that produces alkalilabile sites in DNA, caused damage to both protooncogenes. DNA damage was determined by monitoring the disappearance of specific fragments generated by restriction enzyme digestion in Southern blots. DNA repair in the c-neu and c-myc protooncogenes was examined in confluent cells by measuring the reappearance of these same bands. While the c-neu gene exhibited repair in 24 h, none was detected in the c-myc gene. These results imply that the promutagenic DNA lesions caused by MNNG are differentially repaired in two transcriptionally active genes.
Chary
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Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Mitchell
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Kelly
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D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004848:Epithelium / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000648:ultrastructure; D008745:Methylation; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D009696:Nucleic Acids / Q000302:isolation & purification; D011487:Protein Conformation; D011519:Proto-Oncogenes / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic
D009696:Nucleic Acids; D008769:Methylnitronitrosoguanidine