Metal salts as promoters of in vitro morphological transformation of hamster embryo cells initiated by benzo(a)pyrene.

The hamster embryo cell bioassay has been used to study the effect of metal salts on morphological transformation. A synergistic enhancement of the transformation frequency was found for the combined treatment with organic carcinogens [benzo(a)pyrene, N-hydroxy-2-acetylaminofluorene, and 4-nitroquinoline 1-oxide] and nickel sulfate, cadmium acetate, or potassium chromate. Chromic chloride and zinc chloride did not induce transformation themselves, and they had no effect on the transformation frequency when tested in combination with benzo(a)pyrene. The synergistic effect between benzo(a)pyrene and nickel sulfate or cadmium acetate was also apparent when the cells were treated sequentially with the chemicals. When the cells were first exposed to benzo(a)pyrene, both nickel sulfate and cadmium acetate showed a promotion-like effect similar to that obtained with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Moreover, when 12-O-tetradecanoylphorbol-13-acetate or benzo(a)pyrene were used as promoting agents, both nickel sulfate and cadmium acetate were able to initiate morphological transformation. The data suggest that the metal salts are more potent as promoters than they are as initiators. The present findings may be of importance in relation to carcinogenicity of metal compounds to humans.