Diarrhetic Shellfish Toxin, Dinophysistoxin‐1, Is a Potent Tumor Promoter on Mouse Skin

Dinophysistoxin‐1, 35‐methylokadaic acid, is a causative agent of diarrhetic shellfish poisoning. The biological activities and tumor‐promoting activity of dinophysistoxin‐1 were studied together with those of okadaic acid and 7‐O‐palmitoyl okadaic acid. Dinophysistoxin‐1 is a skin irritant and induces ornithine decarboxylase in mouse skin with the same potency as okadaic acid. 7‐O‐Palmitoyl okadaic acid induced a lower activity than the other compounds. Dinophysistoxin‐1 inhibited the specific [(3)H]okadaic acid binding to a participate fraction of mouse epidermis. The binding affinities of dinophysistoxin‐1 and okadaic acid to a particulate fraction were almost the same. Dinophysistoxin‐1 showed a tumor‐promoting activity as strong as that of okadaic acid in a two‐stage carcinogenesis experiment on mouse skin. The percentages of tumor‐bearing mice in the groups treated with 100 μg of 7,12‐dimethylbenz[α]anthracene (DMBA) followed by 5 μg of dinophysistoxin‐1, twice a week, and with DMBA followed by 5 μg of okadaic acid twice a week were 86.7% and 80.0% in week 30, respectively. The average number of tumors per mouse was 4.6 in the former group and 3.9 in the latter. Dinophysistoxin‐1 and okadaic acid act on cells through different pathways from the 12‐O‐tetradecanoylphorbol‐13‐acetate‐type tumor promoters.