title: Diarrhetic shellfish toxin, dinophysistoxin-1, is a potent tumor promoter on mouse skin.
abstract: 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 [3H]okadaic acid binding to a particulate 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 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) followed by 5 micrograms of dinophysistoxin-1, twice a week, and with DMBA followed by 5 micrograms 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.
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D004790:Enzyme Induction / Q000187:drug effects; D004988:Ethers, Cyclic / Q000378:metabolism; D005260:Female; D007509:Irritants / Q000633:toxicity; D008387:Marine Toxins / Q000633:toxicity*; D051379:Mice; D019319:Okadaic Acid / Q000031:analogs & derivatives; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011714:Pyrans / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: D002273:Carcinogens; D004988:Ethers, Cyclic; D007509:Irritants; D008387:Marine Toxins; D011714:Pyrans; D019319:Okadaic Acid; C051904:dinophysistoxin 1; D015127:9,10-Dimethyl-1,2-benzanthracene; D009955:Ornithine Decarboxylase