Neoplasia in zebrafish (Danio rerio) treated with 7,12-dimethylbenz[a]anthracene by two exposure routes at different developmental stages

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