Dose-Dependent Carcinogenicity and Frequent Ki-ras Proto-oncogene Activation by Dietary N-Nitrosodiethylamine in Rainbow Trout

Hendricks, Jerry D.; Cheng, Ronshan; Shelton, Dennis W.; Pereira, Cliff; Bailey, George S.

doi:10.1006/faat.1994.1078

Cited by 28 publications

(8 citation statements)

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“…The formation of the latter adduct correlates with tumor incidence and is consistent with the dominance of a G -A transition mutation in Ki-ras isolated from these tumors (53,63). This mutagenic specificity probably derives from ineffective alkyltransferase removal of 06-ethylguanine in these animals (53,63). Based on total tumorigenic dosage required, however, Shasta trout and F344 rats show comparable sensitivity to hepatocarcinogenesis by DEN (53).…”

Section: Dna Adduction and Repairsupporting

confidence: 57%

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Fish models for environmental carcinogenesis: the rainbow trout.

Bailey

Williams

Hendricks

1996

Environ Health Perspect

171

114

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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)

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Section: Dna Adduction and Repairsupporting

confidence: 57%

“…Mutational inactivation of the p53 tumor suppressor gene (152) and activation of the ras protooncogene (153) (60), and the Nnitroso compound DEN (53). Table 4 summarizes current knowledge regarding Ki-ras mutational activation among the various tumor types elicited by these and additional carcinogens in trout.…”

Section: Protooncogene Activation In Trout Tumorsmentioning

confidence: 99%

Fish models for environmental carcinogenesis: the rainbow trout.

Bailey

Williams

Hendricks

1996

Environ Health Perspect

171

114

View full text Add to dashboard Cite

show abstract

“…In addition, hepatocellular carcinoma was induced in rivulus by dietary exposure to the antioxidant butylated hydroxyanisole (BHA) (144). Conversely, no neoplasms were seen in rainbow trout in long-term dietary studies with BHA (86). The peroxisome proliferators have also been studied in rainbow trout and medaka, including the hypolipidemic drugs gemfibrozil and ciprofibrate, the plasticizer di(2-ethylhexyl)phthalate (DEHP), and the herbicide 2,4-dichlorophenoxyacetic acid (38,162).…”

Section: Chemicals and Protocolsmentioning

confidence: 99%

“…Ras expression is less common in rat liver neoplasms (189). Goldfish ras was shown to have a 96% homology to human K-ras (136), and point mutations in Ki-ras gene occurred in a high proportion of aflatoxin B1-(41), DMBA-(58), MNNG-(6), and DEN- (86) induced liver tumors in rainbow trout.…”

Section: Molecular Markersmentioning

confidence: 99%

Review Article: Experimental Chemical Carcinogenesis in Fish

Bunton

1996

Toxicol Pathol

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Dr. Bunton's primary research interest is on mechanisms of toxicity and carcinogenesis in fish related to environmental contamination and on the development of alternative models.Experimental carcinogenesis using fish species as alternative models is a dynamic field of research. The 1940's expansion of synthetic chemical producing industries coincided with a number of pollution-associated fish neoplasia epizootics, with polycyclic aromatic hydrocarbons as significant components of contaminated sediment in several cases. Epizootics of primarily liver and skin neoplasia in benthic species near coastal urban or industrial areas indicated the sensitivity of fish species to known mammalian carcinogens. Stressing a mechanistic approach, investigators have used data compiled from epizootics as the backbone of current research efforts to define carcinogenesis in fish species. With liver as the focus, patterns of neoplastic development similar to those seen in rodent bioassays have been induced in various fish species by genotoxic carcinogens. Similarities between fish and rodent models include chemical and species-specific responses to exposure and the development of predictable preneoplastic and neoplastic lesions. The expression of molecular molecules related to carcinogenesis is currently under investigation, which includes alterations in certain proteins, enzyme activity, and oncogene/tumor suppressor gene function. The potential for the application of research findings to both human and environmental health issues makes fish species attractive and valuable alternative models in carcinogenesis and toxicity research.Keywords. Medaka; methylazoxymethanol (MAM); molecular markers; N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); Neoplasia; polycyclic aromatic hydrocarbons (PAH); rainbow trout INTRODUCTION Armed with data from fish neoplasia epizootics related to environmental synthetic chemical contamination, research has moved from the morphologic assessment of neoplasms to the identification of molecular mechanisms of neoplastic development and progression. The value of these studies can be argued along 2 lines that are often, but should not be, separated. One is for application to human health issues for which there is a chronic demand, and the other is the inherent value of monitoring the health of the environment, which includes all of the creatures therein. Unfortunately, it is the latter argument that most often has to be vigorously defended, although minimal reflection will reveal that we, too, are members of this population.The present review discusses experimental fish carcinogenesis by first presenting data from neoplasia epizootics that helped to form the framework of our current 604 research efforts. The effects of known direct and indirect carcinogens on various fish species from laboratory studies are then described to illustrate species similarities and differences in tissue response. The latter portion of the paper concentrates on chemical hepatocarcinogenesis and reviews the histologic and molecular marke...

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“…Activation of K-ras gene has been observed in neoplasms of rainbow trout exposed to aflatoxin B1 (AFB) 14 and diethylnitrosamine (DEN) 15 . In both studies, the mutations were essentially confined to codon 12.…”

Section: Background and Methodsmentioning

confidence: 99%

Novel Mass Spectrometry Mutation Screening for Contaminant Impact Analysis

Cehn¹,

Lee²

2000

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Dose-Dependent Carcinogenicity and Frequent Ki-ras Proto-oncogene Activation by Dietary N-Nitrosodiethylamine in Rainbow Trout

Cited by 28 publications

References 0 publications

Fish models for environmental carcinogenesis: the rainbow trout.

Fish models for environmental carcinogenesis: the rainbow trout.

Review Article: Experimental Chemical Carcinogenesis in Fish

Novel Mass Spectrometry Mutation Screening for Contaminant Impact Analysis

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