title: Neoplasia in zebrafish (Danio rerio) treated with 7,12-dimethylbenz[a]anthracene by two exposure routes at different developmental stages.
abstract: 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.
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis 97331, USA. spitsbej@ucs.orst.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Spitsbergen
authors.forename: H W
authors.initials: HW
authors.lastname: Tsai
authors.forename: A
authors.initials: A
authors.lastname: Reddy
authors.forename: T
authors.initials: T
authors.lastname: Miller
authors.forename: D
authors.initials: D
authors.lastname: Arbogast
authors.forename: J D
authors.initials: JD
authors.lastname: Hendricks
authors.forename: G S
authors.initials: GS
authors.lastname: Bailey
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001835:Body Weight; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000473:pathology; D005880:Gills / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D008648:Mesoderm / Q000187:drug effects / Q000473:pathology; D018204:Neoplasms, Connective and Soft Tissue / Q000139:chemically induced / Q000473:pathology; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000139:chemically induced / Q000473:pathology; D009383:Neoplasms, Vascular Tissue / Q000139:chemically induced / Q000473:pathology; D009432:Neural Crest / Q000187:drug effects / Q000473:pathology; D012744:Sex Ratio; D015027:Zebrafish / Q000196:embryology*
chemical_list: D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene