TitleThe rainbow trout liver cancer model: response to environmental chemicals and studies on promotion and chemoprevention.
Publication TypeJournal Article
Year of Publication2012
AuthorsWilliams DE
JournalComp Biochem Physiol C Toxicol Pharmacol
Date Published2012 Jan
KeywordsAflatoxin B1, Animals, Benzopyrenes, Caprylates, Chemoprevention, Chlorophyllides, Dehydroepiandrosterone, Dose-Response Relationship, Drug, Environmental Exposure, Fluorocarbons, Indoles, Liver, Liver Neoplasms, Experimental, Oncorhynchus mykiss, Promoter Regions, Genetic, Risk Assessment

Rainbow trout (Oncorhynchus mykiss) are an outstanding model of liver cancer induction by environmental chemicals and development of strategies for chemoprevention. Trout have critical and unique advantages allowing for cancer studies with 40,000 animals to determine dose-response at levels orders of magnitude lower than possible in rodents. Examples of two promoters in this model, the dietary supplement dehydroepiandrosterone (DHEA) and industrial chemical perfluorooctanoic acid (PFOA), are presented. In addition, indole-3-carbinol (I3C) and chlorophyllin (CHL) inhibit initiation following exposure to potent human chemical carcinogens (e.g., aflatoxin B(1) (AFB(1))). Two "ED(001)" cancer studies have been conducted, utilizing approximately 40,000 trout, by dietary exposure to AFB(1) and dibenzo[d,e,f,p]chrysene (DBC). These studies represent the two largest cancer studies ever performed and expand the dose-response dataset generated by the 25,000 mouse "ED(01)" study over an order of magnitude. With DBC, the liver tumor response fell well below the LED(10) line, often used for risk assessment, even though the biomarker (liver DBC-DNA adducts) remained linear. Conversely, the response with AFB(1) remained relatively linear throughout the entire dose range. These contributions to elucidation of mechanisms of liver cancer, induced by environmental chemicals and the remarkable datasets generated with ED(001) studies, make important contributions to carcinogenesis and chemoprevention.

Alternate JournalComp. Biochem. Physiol. C Toxicol. Pharmacol.
PubMed ID21704190
PubMed Central IDPMC3219792
Grant ListR01 ES013534-04 / ES / NIEHS NIH HHS / United States
ES013534 / ES / NIEHS NIH HHS / United States
R01 ES013534-03 / ES / NIEHS NIH HHS / United States
R01 ES013534-01A1 / ES / NIEHS NIH HHS / United States
R01 ES013534-02 / ES / NIEHS NIH HHS / United States
R01 ES013534-04S1 / ES / NIEHS NIH HHS / United States
R01 ES013534 / ES / NIEHS NIH HHS / United States