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Neoplasia in Zebrafish (Danio rerio) Treated with 7,12-Diniethylbenz[a]anthracene by Two Exposure Routes at Different Developmental Stages

Departments of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331, Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, Oregon 97331

Hsi-Wen Tsai

Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331

Ashok Reddy

Departments of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331

Tom Miller

Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331

Dan Arbogast

Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331

Jerry D. Hendricks

Departments of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331, Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, Oregon 97331

G.S. Bailey

Departments of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331, Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, Oregon 97331

Using zebrafish, Danio rerio, initial pioneering work in the 1960s revealed carcinogen responsiveness of fish, yet very few subsequent tumorigenesis investigations have utilized this species. We exposed embryos (60 hours postfertilization) and fry (3 week posthatch) to 7,12-dimethylbenz[a]anthracene (DMBA) by immersion in aqueous solutions for 24 hours, at concentrations of 0-1 or 0-5 ppm (mg/L), respectively. Juvenile zebrafish 2 months posthatch were fed a diet containing 0-1,000 ppm DMBA for 4 months. Fish were sampled for histologic evaluation at 7-12 months after the onset of carcinogen treatment. Fry were most responsive to DMBA and showed the widest diversity of target tissues and histologic types of neoplasia, having several types of epithelial, mesenchymal, and neural neoplasia. The principal target tissues for carcinogenic response were liver following embryo or fry exposure, with gill and blood vessel the second and third most responsive tissues in fry. Intestine was the primary target and gill a secondary target in fish that received dietary DMBA as juveniles. These studies indicate that young zebrafish are most responsive to DMBA, showing a greater diversity of neoplasm types than rainbow trout. Thus, zebrafish are a valuable model system in which to study mechanistic aspects of the carcinogenesis process.

Key Words: Carcinogenesis • zebrafish • Danio rerio • tumor • carcinoma • sarcoma • chondrosarcoma • polycyclic aromatic hydrocarbon

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