Active oxygen acts as a promoter of transformation in mouse embryo C3H/10T1/2/C18 fibroblasts.
There is much evidence from in vivo and in vitro carcinogenesis studies that active oxygen species play a role in tumor promotion. We tested directly whether superoxide produced extracellularly by xanthine-xanthine oxidase (X-XO) has the capacity to promote initiated mouse embryo C3H/10T1/2 fibroblasts. Cell cultures initiated with either 137Cs gamma-rays or benzo[a]pyrene diol epoxide I were found to transform 3-30 times more effectively when subsequently treated daily for 3 weeks with nontoxic doses of X-XO. Scavengers of active oxygen radicals such as superoxide dismutase or superoxide dismutase in combination with catalase reduced the frequency of appearance of transformed foci by 3-25 times when compared to cultures receiving X-XO alone. These results show that active oxygen species such as superoxide and H2O2 can act in a promotional manner that mimics the effects of the mouse skin promoter phorbol 12-myristate 13-acetate in this system. X-XO also acted as a weak complete carcinogen.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology; D005720:Gamma Rays; D051379:Mice; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000633:toxicity*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D019820:Xanthine; D014969:Xanthine Oxidase; D014970:Xanthines
D001580:Benzopyrenes; D002273:Carcinogens; D014970:Xanthines; D019820:Xanthine; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D014969:Xanthine Oxidase; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen