Fish models for environmental carcinogenesis: the rainbow trout.

Abstract

Progress over the past 30 years has revealed many strengths of the rainbow trout as an alternative model for environmental carcinogenesis research. These include low rearing costs, an early life-stage ultrasensitive bioassay, sensitivity to many classes of carcinogen, a well-described tumor pathology, responsiveness to tumor promoters and inhibitors, and a mechanistically informative nonmammalian comparative status. Low-cost husbandry, for example, has permitted statistically challenging tumor study designs with up to 10,000 trout to investigate the quantitative interrelationships among carcinogen dose, anticarcinogen dose, DNA adduct formation, and final tumor outcome. The basic elements of the trout carcinogen bioassay include multiple exposure routes, carcinogen response, husbandry requirements, and pathology. The principal known neoplasms occur in liver (mixed hepatocellular/cholangiocellular adenoma and carcinoma, hepatocellular carcinoma), kidney (nephroblastoma), swim bladder (adenopapilloma), and stomach (adenopapilloma). Trout possess a complex but incompletely characterized array of cytochromes P450, transferases, and other enzymic systems for phase and phase 11 procarcinogen metabolism. In general, trout exhibit only limited capacity for DNA repair, especially for removal of bulky DNA adducts. This factor, together with a high capacity for P450 bioactivation and negligible glutathione transferase-mediated detoxication of the epoxide, accounts for the exceptional sensitivity of trout to aflatoxin B1 carcinogenesis. At the gene level, all trout tumors except nephroblastoma exhibit variable and often high incidences of oncogenic Ki-ras gene mutations. Mutations in the trout p53 tumor suppressor gene have yet to be described. There are many aspects of the trout model, especially the lack of complete organ homology, that limit its application as a surrogate for human cancer research. Within these limitations, however, it is apparent that trout and other fish models can serve as highly useful adjuncts to conventional rodent models in the study of environmental carcinogenesis and its modulation. For some problems, fish models can provide wholly unique approaches.Environ Health Perspect 104(Suppl 1): 5-21 (1996)

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

“…Investigations of the causes of epizootics of skin and liver neoplasia occurring in fish from polluted environments have most often implicated polycyclic aromatic hydrocarbons (PAHs) as etiologic agents (19). Among numerous fish species studied, the most complete and detailed mechanistic and dose-response studies regarding a wide array of carcinogens have been performed in rainbow trout (4). Various small aquarium fish species have been utilized as carcinogenesis models including the guppy, sheepshead minnow, Rivulus, and medaka (7,24,33).…”

“…Following aqueous exposure to DMBA as fry, stomach, liver, gas bladder, and kidney are target tissues, with decreasing incidences of epithelial neoplasia in these tissues in the order listed (15,20). Dietary exposure of rainbow trout to DMBA results in primarily gastric neoplasia and lesser incidences of liver and gas bladder neoplasia (4). A single mesenchymal neoplasm, a fibrosarcoma of the liver, occurred in rainbow trout administered BAP by intraperitoneal injection at 10 months of age (27) (20).…”

Aeromonas hydrophila in tilapia (Oreochromis niloticus) after the intake of aflatoxins

“…The sensitivity of fish to mycotoxins is variable, and the rainbow trout species exhibits more sensitivity (Bailey et al, 1996). Arana et al (2002) showed that the trout genotype can significantly affect the effect of aflatoxins on growth parameters and weight gain.…”

Neuronal Embryonal Tumors in Fish

“…Some well-documented neoplasms include viral-induced dermal sarcomas in walleyes and aflatoxin-associated hepatocellular adenomas and carcinomas in rainbow trout as well as a variety of sporadic tumors in numerous species. 1,2,12 This report details spontaneous ocular and cutaneous tumors in multiple fresh and marine teleost species with features characteristic of neuronal embryonal tumors.Neuronal embryonal tumors arise from neuroectodermal progenitor cells within subependymal matrix layers and have morphology and aggressive behavior in common.10 Tumor types include medulloepitheliomas, neuroblastomas, retinoblastomas, ependymoblastomas, and primitive neuroectodermal tumors (PNETs). PNETs are derived from pluripotent germinal neuroepithelial cells and may be further classified on the basis of anatomic location as medulloblastomas, cerebral PNETs, or peripheral neuroectodermal tumors.…”

“…Some well-documented neoplasms include viral-induced dermal sarcomas in walleyes and aflatoxin-associated hepatocellular adenomas and carcinomas in rainbow trout as well as a variety of sporadic tumors in numerous species. 1,2,12 This report details spontaneous ocular and cutaneous tumors in multiple fresh and marine teleost species with features characteristic of neuronal embryonal tumors.…”