Unscheduled DNA synthesis in human oral mucosa treated with chemical carcinogens in short-term organ culture.
Unscheduled DNA synthesis (UDS) was investigated by autoradiography in human oral mucosa treated with 10 representative chemical carcinogens. Small sections of gingiva in short-term organ culture were exposed for 2 hours to chemical carcinogens plus [methyl-3H]thymidine. Significant numbers of silver grains, indicating UDS, were detected over the nuclei of both epithelial cells and fibroblasts. All ultimate or proximate carcinogens tested induced UDS. Of five procarcinogens tested, only benzo[a]pyrene (BP) did not induce UDS, but the more activated metabolite of BP, (+/-)-trans-7 beta-8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE I), was very effective in inducing UDS. Ultimate or proximate carcinogens induced higher levels of UDS than did procarcinogens. All the carcinogens that induced UDS showed clear dose-dependent effects. UDS levels were twofold to fivefold higher in the epithelial cells than in the fibroblasts, regardless of the type of carcinogen tested. Comparisons of the levels of UDS induced by 4-(hydroxyamino)quinoline 1-oxide, methyl methanesulfonate, or BPDE I did not reveal any significant differences. These findings indicate that human gingival epithelial UDS assay should be useful for short-term detection of environmental carcinogens that induce cancer in human oral mucosa.
D001345:Autoradiography; D002273:Carcinogens / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D013997:Time Factors
D002273:Carcinogens; D004247:DNA