Promotion of C3H/10T1/2 morphological transformation by polychlorinated dibenzo-p-dioxin isomers.
Few of the seventy-five chlorinated dibenzo-p-dioxin isomers present in the environment have been adequately characterized for their carcinogenic potential. In previous studies we observed that the carcinogenic dioxin isomer 2,3,7,8-tetrachlorodibenzo-p-dioxin promoted cell transformation when continuously applied to C3H/10T1/2 cells initiated by treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The current study was undertaken to evaluate the response of the C3H/10T1/2 cell transformation system to several other dioxin isomers of known carcinogenic potential. 1,2,3,6,7,8- and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin (HCDD) (1-1000 nM) and 2,7-dichlorodibenzo-p-dioxin (0.1-20 microM) failed to transform C3H/10T1/2 cells or to initiate transformation in cultures subsequently treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Continuous exposure of MNNG-initiated cultures to 2,7-DCDD (1-5000 nM) produced elevated but not statistically significant numbers of transformed foci at the highest dose tested. 1,2,3,6,7,8- and 1,2,3,7,8,9-HCDD were promoters of transformation when applied at concentrations greater than or equal to 12 and 40 pM, respectively, to C3H/10T1/2 cultures initiated with MNNG. Maximum responses for both HCDD isomers were attained at concentrations between 120 and 400 pM. These studies suggest that the C3H/10T1/2 cell transformation system may provide a relevant in vitro model for the identification and study of carcinogenic dioxin isomers.
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004147:Dioxins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009152:Mutagenicity Tests; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000494:pharmacology*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D008769:Methylnitronitrosoguanidine; C000925:2,7-dichlorodibenzo-4-dioxin