Reactivity of Tissue-Specific Antigens in N-Methyl-N'-Nitro-N-Nitrosoguanidine-Induced Neoplasms and Normal Tissues from Medaka (Oryzias latipes)*<sup>1</sup>

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To test the sensitivity of the small fish species Oryzias latipes to the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), medaka were exposed at 15 days of age to 30 mg/L for 1 hr and followed for up to 16 mo. One hundred neoplasms were diagnosed in 84 of 213 exposed fish, with approximately equal percentages in males and females. Many neoplasms (62%) were of mesenchymal origin and were categorized as blood vascular neoplasms (hemangioma and hemangiosarcoma), invasive sarcomas, and scale-associated neoplasms. Invasive sarcomas included rhabdomyosarcoma, fascial sarcoma, hemangiopericytoma, and undifferentiated sarcoma. A scale-associated neoplasm, termed lepidocytoma, was an unusual neoplasm of scale anlage. Thyroid follicular neoplasms, with a 100% incidence in males, and pancreatic acinar carcinoma were the most common epithelial tumors. Neoplasms of the gills, swim bladder, and olfactory epithelium were also seen as well as teratoma with mixed epithelial and mesenchymal components. The study showed a broad range of neoplasms induced by MNNG in medaka, with a tissue distribution that might support direct action on exposed tissues.

Section: Neoplasms Of Epithelial Originmentioning

confidence: 93%

“…Medaka (Oryzias latipes) were housed and maintained in accordance to the established standard operating procedures (6) (12,13). Liver tissue from one case described in this (Fig.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

N-Methyl-N'-Nitro-N-Nitrosoguanidine-Induced Neoplasms in Medaka (Oryzias latipes)*¹

Bunton

Wolfe

1996

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“…Other novel oncogene/tumor suppressor genes may also exist in fish species, and their existence and roles in carcinogenesis need to be explored (204 (31-33, 37, 198). Other markers, such as actin and S-100 proteins (35,37,199), also appear to be conserved. Carcinoembryonic antigen, a glycoprotein found in embryonic intestinal tract and liver, was recently labeled in biliary neoplasms from DEN-exposed rivulus (196), and a-fetoprotein-like immunoreactivity was elevated in rainbow trout sera from fish with aflatoxin B 1-induced hepatocellular carcinoma (160).…”

Section: Molecular Markersmentioning

confidence: 99%

Review Article: Experimental Chemical Carcinogenesis in Fish

Bunton

1996

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...

“…Similarly, several articles have referred to detection of proliferating cell nuclear antigen (PCNA) or p53 in fish tissues (14,15,18,23,30,34,38 (26). MNNG has been used frequently in fish to induce neoplasia in liver and other tissues (5,6,16).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis, PCNA, and p53 in Fundulus grandis Fish Liver after In Vivo Exposure to N-methyl-N'-nitro-N-nitrosoguanidine and 2-Aminofluorene

Blás-Machado

Means

2000

Dysfunction in homeostatic mechanisms of cell death and proliferation are considered to be important in the pathogenesis of chemically induced neoplasia. p53 has been implicated in the regulation of cell death and proliferation. To determine whether expression of apoptosis, proliferating cell nuclear antigen (PCNA), and p53 differ between an alkylating agent and a polycyclic aromatic hydrocarbon, host response was measured through sequential immunohistochemical detection of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method), PCNA PC-10, and p53 (PAb 240) in livers of the fish Fundulus grandis. Nine hundred fish were randomly assigned to 3 groups of 300 fish each and kept in separate aquarium tanks. One group of fish was exposed to 6.7 μM N -methyl-N' -nitro-N -nitrosoguanidine (MNNG), 1 group was exposed to 6.9 mM 2-aminofluorene (2-AF), and the remaining group served as a control. A significant decrease (p = 0.005) in the level of apoptosis and a significant increase (p < 0.0001) in the level of p53 were found on experimental day 180 in the livers of MNNG-exposed fish. PCNA was significantly increased (p < 0.005) by day 9 of the experiment in both MNNG and 2-AF fish when compared with controls, but no significant differences existed between the 2 groups of treated fish. Response of fish liver cells to MNNG-mediated and 2-AF-mediated injury differs, at least initially, in the expression of p53, inhibition of apoptosis, and increased net cell proliferation. Concurrent use of a marker for cell death with a marker of proliferation greatly enhances the assessment of the effect of these compounds on liver cells.