Promotion of C3H/10T1/2 morphological transformation by polychlorinated dibenzo-p-dioxin isomers

Few of the seventy-five chlorinated dibenzo-p-dioxin isomerspresent in the environment have been adequately characterizedfor their carcinogenic potential. In previous studies we observedthat the carcinogenic dioxin isomer 2,3,7,8-tetra-chlorodibenzo-p-dioxinpromoted cell transformation when continuously applied to C3H/10T1/2cells initiated by treatment with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). The current study was undertaken to evaluate the responseof the C3H/10T1/2 cell transformation system to several otherdioxin isomers of known carcinogenic potential. 1,2,3,6,7,8-and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin (HCDD) (1–1000nM) and 2,7-dichlorodibenzo-p-dioxin (0.1–20 µM)failed to transform C3H/10T1/2 cells or to initiate transformationin cultures subsequently treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate.Continuous exposure of MNNG-initiated cultures to 2,7-DCDD (1–5000nM) produced elevated but not statistically significant numbersof 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 appliedat concentrations 12 and 40 pM, respectively, to C3H/10T1/2cultures initiated with MNNG. Maximum responses for both HCDDisomers were attained at concentrations between 120 and 400pM. These studies suggest that the C3H/10T1/2 cell transformationsystem may provide a relevant in vitro model for the identificationand study of carcinogenic dioxin isomers.