Chapter 36 – Cancer

Publisher Summary Fish have been studied as a model both for the mechanics of cancer initiation and for progression, and for a model of environmental risk caused by carcinogens in aquatic ecosystems. This chapter focuses on two most widely used species—medaka (Oryzias latipes), and rainbow trout (Oncorhynchus mykiss). The advantages of these models are also discussed. Medaka is an ideal test species; small size and high tolerance to marginal water quality allow medaka to be housed in high density, increasing statistical power at the same time lowering maintenance costs and decreasing the amount of carcinogen needed to conduct studies. Small size also decreases costs associated with histological processing, allowing complete survey of major organs on a single slide and, with serial sections, morphometric analysis. Early maturation and sexual dimorphism allow for manipulation of gender to assess sex-linked and hormonal influences, and continuous spawning ensures year-round availability. Key advantage with medaka is a short time to tumor. Latency periods following brief carcinogen exposure are of the order of months. With longer exposure protocols, tumor induction can take as little as 6 weeks. And unlike many rodent models, spontaneous neoplasms are rare in medaka. Tumor cell lines have been established from carcinogen-induced neoplasms and inbred strains developed to study tumor pathogenesis with transplantation experiments. Rainbow trout are initially recognized as potential test animals following accidental induction of liver tumors with aflatoxin-contaminated feeds. The trout model clearly holds an advantage with respect to: assessment of carcinogen uptake and metabolism; correlation of data from individual lesions; and studies assessing the impact of tumor modulators.