Autoradiographic demonstration of DNA repair synthesis in rat tracheal epithelium treated with chemical carcinogen in vitro.
A system in which tracheal organ culture of inbred F344 rats was used in combination with autoradiography was developed for quantitative measurement of DNA repair synthesis in tracheal epithelial cells. Small sections of trachea in short-term organ culture were treated with various carcinogens plus [methyl-3H]thymidine. Significant numbers of grains, indicating DNA repair, were detected on the nuclei of epithelial cells of tracheal sections treated with carcinogens, and the numbers were proportioned to the concentrations of the carcinogens. The nuclear [methyl-3H]thymidine labeling index (S-phase index) was approximately 0.02, and this did not interfere appreciably with quantitative grain counting. This autoradiographic method is suitable for quantitative measurement of DNA repair synthesis in epithelial cells of the trachea in conditions mimicking those in vivo. These results suggest the potential use of this system for studies on the mechanism of carcinogenesis at a cellular level in keeping with recent biochemical studies on metabolism of carcinogens in respiratory organs in culture. The system may also be useful for screening environmental chemicals suspected of damaging DNA of the respiratory organs in relation to lung carcinogenesis.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D002273:Carcinogens / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D005038:Ethylnitrosourea / Q000494:pharmacology; D008297:Male; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical; D014132:Trachea / Q000187:drug effects*
D002273:Carcinogens; D015112:4-Nitroquinoline-1-oxide; D008741:Methyl Methanesulfonate; D005038:Ethylnitrosourea