title: Dehydroepiandrosterone is a complete hepatocarcinogen and potent tumor promoter in the absence of peroxisome proliferation in rainbow trout.
abstract: Dehydroepiandrosterone (DHEA), fed for 30 weeks to rainbow trout after initiation with the hepatocarcinogen aflatoxin B1 (AFB1), produced a dose-dependent enhancement of carcinogenesis as measured by increased tumor incidence, multiplicity and size. Significant enhancement was observed at 222 p.p.m., which corresponds to a daily dosage one-half that previously administered to humans in clinical trials. DHEA was also capable of acting as a complete carcinogen in this model, producing liver tumors at doses as low as 222-444 p.p.m. Tumors isolated from trout treated with DHEA alone contained mutations in Ki-ras, primarily codon 12[1] G-->A transitions, providing the first suggestive evidence that DHEA could be a genotoxic carcinogen. The carcinogenicity of DHEA in trout is independent of peroxisome proliferation, as measurements of peroxisomal beta-oxidation and catalase activity support previous observations that trout, like humans, are weak responders to peroxisome proliferators.
authors.affiliation: Toxicology Program, Oregon State University, Corvallis 97331-6602, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Orner
authors.forename: C
authors.initials: C
authors.lastname: Mathews
authors.forename: J D
authors.initials: JD
authors.lastname: Hendricks
authors.forename: H M
authors.initials: HM
authors.lastname: Carpenter
authors.forename: G S
authors.initials: GS
authors.lastname: Bailey
authors.forename: D E
authors.initials: DE
authors.lastname: Williams
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D003687:Dehydroepiandrosterone / Q000633:toxicity*; D011905:Genes, ras; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics; D008830:Microbodies / Q000187:drug effects*; D009154:Mutation; D017686:Oncorhynchus mykiss
chemical_list: D002273:Carcinogens; D003687:Dehydroepiandrosterone; D016604:Aflatoxin B1