Detection of chemical carcinogens by assay of unscheduled DNA synthesis in rat tracheal epithelium in short-term organ culture.
A short-term organ culture of rat tracheal epithelium was used to detect the ability of 53 chemicals to induce UDS. In this system all direct-acting compounds (ultimate or proximate carcinogens) tested induced UDS. Of 24 compounds requiring metabolism (procarcinogens), nine induced UDS, viz., 4NQO, AF-2, BP, DMN, DEN, and NP. Urethane, AAF, and 2,7-AAF induced very slight UDS. 3-Methyl-4NQO for which carcinogenicity data is incomplete as positive in our system. Among the cancer chemotherapeutic agents tested only mitomycin C induced UDS. MC and DMBA, which are known to induce cancer of respiratory organs in experimented animals, and DAB, aflatoxin B1 and Trp-P-1, which are strong carcinogens in the liver, did not induce UDS within 2 h. With the longer exposure (24 h), these carcinogens also failed to elicit UDS. All the carcinogens that induce UDS showed clear dose-dependent effects. No non-carcinogens tested induced UDS. These results suggested that this system should be useful for screening environmental chemicals suspected of damaging DNA of the respiratory organ on the basis of organotropic effects for UDS induction in cultured rat tracheal epithelium.
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis*; D004353:Drug Evaluation, Preclinical; D004848:Epithelium / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D011916:Rats, Inbred F344; D012142:Respiratory Tract Neoplasms / Q000139:chemically induced; D014132:Trachea / Q000378:metabolism*
D002273:Carcinogens; D004247:DNA