Fish models for environmental carcinogenesis: The rainbow trout

被引:163
作者
Bailey, GS
Williams, DE
Hendricks, JD
机构
[1] Dept. of Food Science and Technology, Mar./Freshw. Biomed. Sciences Center, Oregon State University, Corvallis, OR
[2] Dept. of Food Science and Technology, Mar./Freshw. Biomed. Sciences Center, Oregon State University, Corvallis
关键词
trout; carcinogenesis; neoplasms; oncogenes; DNA adducts; fish models;
D O I
10.2307/3432693
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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 I and phase II 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 B-1 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.
引用
收藏
页码:5 / 21
页数:17
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