Promotion of BALB/3T3 Cell Transformation by the Okadaic Acid Class of Tumor Promoters, Okadaic Acid and Dinophysistoxin‐1

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Abstract
Okadaic acid and dinophysistoxin‐1 are non‐12‐O‐tetradecanoylphorbol‐13‐acetate (non‐TPA)‐type tumor promoters, which enhance chemically induced tumorigenesis on mouse skin through a different mechanism from that of TPA. In the present study, we examined the promoting effects of these okadaic acid class tumor promoters on a two‐stage transformation using BALB/3T3 cells which was designed to simulate in vivo two‐stage carcinogenesis. Cells were treated first with a low dose of the initiator 3‐methylcholanthrene (MCA) and then with a test chemical. Okadaic acid and dinophysistoxin‐1 significantly enhanced the MCA‐induced cell transformation. Okadaic acid tetramethyl ether, an inactive compound, did not affect the transformation of MCA‐treated cells. The okadaic acid class of tumor promoters failed to induce transformation without pretreatment by MCA. Okadaic acid did not show initiating activity in the two‐stage transformation assay in which cells were treated first with okadaic acid and then with TPA. These results indicate that this transformation assay with BALB/ 3T3 cells is useful to predict tumor‐promoting activity of non‐TPA‐type as well as TPA‐type tumor promoters, before long‐term in vivo two‐stage carcinogenesis experiments are carried out.

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