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Thirteen cases of proliferative lesions of the swimbladder were encountered in Japanese medaka Oryzias latipes and guppy Poecilia reticulata from about 10,000 medaka and 5,000 guppies used in carcinogenicity tests and histologically examined. Two of the four cases from medaka and eight of the nine from guppies occurred in untreated control specimens. The lesions affected the gas gland epithelium and included hyperplasia, adenoma, and adenocarcinoma. One medaka had hyperplasia of the gas gland epithelium and in one guppy the gland was enlarged with an increase in the number of epithelial layers. Gas gland adenomas, three cases in medaka and one in the guppy, were typically larger than the hyperplastic lesions formed expansive masses up to 1 mm in greatest dimension, and exhibited a solid or glandular growth pattern and mild cellular pleomorphism. Adenocarcinoma was the most advanced lesion and all seven cases occurred in guppies. Adenocarcinomas sometimes filled the entire swimbladder and measured up to 2.5 mm in diameter. Cells of adenocarcinomas were highly pleomorphic, with atypical nuclei, and an elevated mitotic activity. Because most of these tumors occurred in fish from control groups or in tests with noncarcinogenic compounds, the lesions observed here are probably spontaneous rather than chemically-induced. Their rare occurrence, however, makes swimbladder proliferative lesions in small fish carcinogenesis models sensitive indicators of compounds that might target cells of the gas gland.

Fournie, John W., Marilyn J. Wolfe, Jeffrey C. Wolf, Lee A. Courtney, Rodney D. Johnson and William E. Hawkins. 2005. Diagnostic Criteria for Proliferative Thyroid Lesions in Bony Fishes. Toxicol. Pathol. 33(5):540-551. (ERL,GB 1224).

Thyroid proliferative lesions are rather common in bony fishes but disagreement exists in the fish pathology community concerning diagnostic criteria for hyperplastic versus neoplastic lesions. To simplify the diagnosis of proliferative thyroid lesions and to reduce confusion regarding lesion interpretation, we propose specific criteria for distinguishing hyperplastic from neoplastic lesions. Development of these criteria was based on the examination of a large series of proliferative lesions from Japanese medaka (Oryzias latipes), lesions from other small fish species, and a reexamination of the 97 cases of proliferative thyroid lesions from bony fishes deposited in the Registry of Tumors in Lower Animals. Specific diagnostic criteria are provided for all lesion categories including follicular cell hyperplasia (simple, nodular, or ectopic), adenoma (papillary or solid), and carcinoma (well- or poorly differentiated).These criteria should assist fish pathologists in describing and categorizing naturally-occurring proliferative lesions from wild fishes, lesions that develop in laboratory fishes due to suboptimal culture practices or water quality, those in fishes used in toxicological assays, and captive aquarium fishes.

Blazer, Vicki S., John W. Fournie, Jeffrey C. Wolfe and Marilyn J. Wolfe. 2006. Diagnostic Criteria for Proliferative Hepatic Lesions in Brown Bullhead. Dis. Aquat. Org. 72(1):19-30. (ERL,GB 1256).

Brown bullhead Ameiurus nebulosus have been used as indicator species for contaminant effects at Areas of Concern (AOC) in the Great Lakes and other areas. One of the beneficial use impairments at numerous AOC is “fish tumors and other deformities”. An impairment occurs when the incidence of fish tumors and other deformities exceeds rates at unimpacted or control sites or when survey data confirm the presence of neoplastic or preneoplastic liver tumors in bullhead or suckers. Numerous surveys have been conducted over the years assessing both liver and skin tumors (neoplasia). However, a major problem in comparing the results has been a lack of consistent criteria for evaluating histological changes in bullhead livers. As AOC develop and implement remedial action plans realistic and attainable delisting targets need to be specified. For this to occur and be consistent from site to site there must be standardization of the criteria being used to evaluate specific impairments. The purpose of this report is to describe and illustrate the proliferative liver lesions in bullhead and suggest a classification system for these lesions.

Couch, John A. 1976. Attempts to Increase Baculovirus Prevalence in Shrimp by Chemical Exposure. In: Tumors in Aquatic Animals. Clyde J. Dawe, Dante G. Scarpelli, and Sefton R. Wellings, Editors. S. Karger, Basel. 20:304-314. (ERL,GB 240). (Progress in Experimental Tumor Research; v. 20)

Little information is available concerning interactions between pollutant chemicals and viruses in aquatic animals. Samples of pink shrimp (Penaeus duorarum) with various enzootic levels of a natural baculovirus infection were experimentally exposed to low levels of Aroclor 1254, a polychlorinated biphenyl (PCB), mirex, cadmium, and methoxychlor in the laboratory. No consistent pattern of increase in prevalence of virus was found, and no indication of tumor induction was detected.

Couch, John A. and W. Peter Schoor. 1982. Effects of Carcinogens, Mutagens, and Teratogens on Non-Human Species (Aquatic Animals). In: Proceedings of the Second NCI/EPA/NIOSH Collaborative Workshop: Progress on Joint Environmental and Occupational Cancer Studies, September 9-11, 1981, Rockville, MD. Herman F. Kraybill, Ingeborg C. Blackwood, and Nancy B. Freas, Editors. U.S. Government Printing Office, Washington, DC. Pp. 688-726. (ERL,GB 433). (May, 1980 - October, 1981)

Aquatic systems and organisms are under examination in order to develop indicator, screening, and modeling capabilities for detection of carcinogens, mutagens and teratogens. In the third year of the program, several advances were made in the development of assays, utilizing sheepshead minnows (liver lesions via benzidine and aflatoxin exposure), rainbow trout (liver tumors via benzo(a)pyrene exposures), and freshwater catfish (papillomatous-like lesions via chlorinated effluent exposures). Results of long-term exposures of fish to the herbicide trifluralin show that induced boney growths are accompanied by histopathologic changes of the pituitary. These and other studies continue to reveal that fish have metabolic pathways similar to mammals for disposition of certain carcinogens. A significant number of cooperative agreements with principal investigators support an extramural complemental and supplemental effort in the identification of aquatic species and systems that may serve as early warning mechanisms.

Courtney, Lee A. and John W. Fournie. 1991. Ocular Chondrosarcomas in Rivulus marmoratus Poey. EPA/600/J-91/101. J. Fish Dis. 14(1):111-116. (ERL,GB 679). (Avail. from NTIS, Springfield, VA: PB91-206946)

Only one documented case of a malignant cartilaginous tumor has been previously reported from fish, a large cranial chondrosarcoma from the paddlefish, Polyodon spathula (Walbaum). Described here are two chondrosarcomas diagnosed from adult laboratory-reared Rivulus marmoratus Poey, the first reports of this tumor type from an atheriniform fish. Histologically, the tumors consisted of cartilage in various stages of differentiation. These ranged from poorly differentiated areas consisting of a highly cellular, primitive mesenchymal component with numerous mitotic figures and extensive anaplasia to well-differentiated portions expressed as scattered foci of mature cartilage consisting of single and multiple chondrocytes isolated within lacunae. The lesions, possibly arising from the sclera, were invasive into the eye, with elements of the choroid and striated muscle trapped within the tumor matrix. Histologically these lesions resemble the paddlefish chondrosarcoma and mesenchymal chondrosarcomas in higher vertebrates.

Hawkins, William E., John W. Fournie, Michael St.J. Battalora and William W. Walker. 1991. Carcinoma of the Exocrine Pancreas in Medaka. EPA/600/J-91/341. J. Aquat. Anim. Health. 3:213-220. (ERL,GB 715). (Avail. from NTIS, Springfield, VA: PB92-129782)

Eight cases of acinar cell carcinoma of the exocrine pancreas were diagnosed in Japanese medaka (Oryzias latipes) from a pool of approximately 10,000 specimens used in carcinogenesis tests of a variety of compounds. Three cases occurred in speciments from control groups and one case in a specimen treated with benzo[e]pyrene, a noncarcinogenic isomer of benzo[a]pyrene. Four cases occurred in specimens treated with compounds that were carcinogenic to medaka. These included two cases in specimen treated with 7,12-dimethylbenz[a ]anthracene, one treated with benzo[a]pyrene, and one treated with methylazoxymethanol acetate. Pancreatic carcinoma was likely to have been the cause of death in each of the five cases. The neoplasms appeared to originate in the abdominal mesentery. Tumor cells infiltrated the peritoneal cavity and retroperitoneal spaces, invading the gonads, intestine, and kidney. In several cases, the tumors metastasized through the blood, as evidenced by tumor emboli in the heart and tumor cells trapped along trabeculae of the atrial myocardium. Tumor cells, which we believe were of acinar cell origin, were basophilic and poorly differentiated, had a high nucleus-to-cytoplasm ratio, exhibited numerous mitoses, and tended to form cords and lobules. Based on the scattered occurrence of the tumors and the fact that a concentration-response relationship was not evident even in those cases developing after exposure to strong carcinogens, we consider the lesion to be spontaneous.

Folmar, L.C., J. Harshbarger, P.C. Baumann, G. Gardner and S. Bonomelli. 1995. Pathological and Serum Chemistry Profiles of Brown Bullheads (Ameiurus nebulosus) from the Black River and Old Woman Creek, Ohio. Bull. Environ. Contam. Toxicol. 54(1):50-59. (ERL,GB 842).

This study compares serum chemistry values for brown bullheads (Ameiurus nebulosus) from the industrially contaminated Black River, Ohio, with the rural and relatively uncontaminated Old Woman Creek, Ohio. Fifty-two percent (24 of 46) brown bullheads over 3-years-old had liver neoplasms: 30% (14) were of hepatocellular origin, not including 17% (8) that had foci of hepatocellular alteration and 48% (22) of cholangiocellular origin. Eleven fish had both types of liver tumors. In addition to liver tumors, four fish had squamous cell carcinomas, one had an epidermal papilloma and one had a mesothelioma. Only 1 of the 30 reference fish had a neoplasm of any type, a low grade cholangiocellular carcinoma. Of the 20 serum parameters measured, the mean values of nine were significantly different between the two populations. Seven of the nine were higher in the Black River fish (alanine and aspartate aminotransferase, lactate dehydrogenase, total protein, blood urea nitrogen, triglycerides and calcium). In contrast, manganese and inorganic phosphate were significantly lower. However, in individual fish, none of the serum parameters were significantly correlated with either type of liver neoplasm or either parasitosis.

Denslow, Nancy D., Ming M. Chow and Leroy C. Folmar. 1994. Isoforms of Apolipoprotein A-I in the Serum of Brown Bullheads (Ameiurus nebulosus) with Liver Cancer. Can. J. Zool. 72(8):1522-1527. (ERL,GB 853).

Brown bullheads (Ameiurus nebulosus) express two different isoforms of apolipoprotein A-I in the serum, a predominant form characterized by a pI of 6.9 and a more acidic isoform with a pI of 6.65. The two proteins were identified by N-terminal amino acid sequencing, with 50 residues for the pI 6.9 isoform and 20 residues for the pI 6.65 isoform. Sequences for the two proteins were identical for the first 20 amino acids; however, differences in their primary sequences were deduced by analysis of peptide maps obtained through proteolytic digestion. The ratio of the isoforms changes from 75% pI 6.9/25% pI 6.65 (no tumors) to equal amounts of both isoforms in bullheads with hepato- or cholangio-cellular carcinomas. This is the first report of these serum isoforms in feral fish showing that the expression of these proteins is directly related to both cholangio- and hepato-cellular carcinomas. The potential use of these proteins as tumor biomarkers is discussed.

Diamant, Ariel, John W. Fournie and Lee A. Courtney. 1994. X-Cell Pseudotumors in a Hardhead Catfish, Arius felis (Ariidae), from Lake Pontchartrain, Louisiana, U.S.A.. EPA/600/J-94/340. Dis. Aquat. Org. 18:181-185. (ERL,GB 856). (Avail. from NTIS, Springfield, VA: PB94-198165)

X-cell epidermal lesions are described from a single specimen of the hardhead catfish Arius felis (Aridae). The lesions exhibited an unusual growth pattern but did not involve any visceral organs. Histologically, the lesions resembled those previously described for coldwater fishes. This is the first report of X-cell lesions from Lake Pontchartrain, Louisiana, USA, and the hardhead catfish represents the first warmwater species affected with the disease.

Vogelbein, W.K., D.E. Zwerner, M.A. Unger, C.L. Smith and J.W. Fournie. 1997. Hepatic and Extrahepatic Neoplasms in a Teleost Fish from a Polycyclic Aromatic Hydrocarbon Contaminated Habitat in Chesapeake Bay, USA. In: Spontaneous Animal Tumors: A Survey. Proceedings of the First World Conference on Spontaneous Animal Tumors, Genoa, Italy. Lorenzo Rossi, Ralph Richardson, and John Harshbarger, Editors. Press Point di Abbiategrasso, Milano, Italy. Pp. 55-63. (ERL,GB 932).

The mummichog, Fundulus heteroclitus, is one of the most abundant teleost fishes inhabiting salt marshes of the Atlantic coast of North America. Although the geographic range of this small cyprinodontid extends from Nova Scotia, Canada, to northern Florida, USA, local subpopulations are thought to be largely non-migratory. This, and it's adaptability to laboratory conditions, has led to the increasing use of this species as a bioassay organism in aquatic toxicology and as a sentinel of environmental quality. We recently reported high prevalences of liver neoplasms and associated lesions in mummichog inhabiting a polycyclic aromatic hydrocarbon (PAH) contaminated environment in Virginia, USA. This site is adjacent to a wood treatment facility that has treated railroad ties, pilings, and telephone poles with creosote and pentachlorophenol since the late 1920s. In 1991, this facility was placed into the U.S. Environmental Protection Agency's (EPA) Superfund Program and wood treatment operations were suspended. However, the property continues to be used to store timbers, and the adjacent aquatic habitat remains heavily contaminated. In addition to the hepatocellular neoplasms, mummichog from this site also exhibit elevated prevalences of neoplasms derived from biliary, exocrine pancreatic, vascular, lymphoid, and renal tissues. The extremely high PAH concentrations in sediments at this site (e.g., 2200 mg/kg dry wt), the diversity of the tumorigenic response, and the absence of neoplasms in fish from a mildly contaminated habitat only about 0.5 km away have suggested a chemical etiology for these lesions. Histopathology has recently gained acceptance in several U.S. pollution monitoring programs, and morphologic characterizations of tissue alterations in fish from polluted habitats have been given a high priority. The objective of this communication is to report histology and prevalence data for the hepatic and extra-hepatic proliferative lesions and neoplasms observed in mummichog from the above described creosote-contaminated environment.

Martin, B.J. 1980. Effects of Petroleum Compounds on Estuarine Fishes. EPA-600/3-80-019. U.S. Environmental Protection Agency, Environmental Research Laboratory, Gulf Breeze, FL. 31 p. (Avail. from NTIS, Springfield, VA: PB80-141310)

Effects of the carcinogenic polycyclic aromatic hydrocarbons (pah), benzo(a)pyrene (bap), and methylcholanthrene (mca) were investigated with sheepshead minnows (cyprinodon variegatus) and channel catfish (ictalurus punctatus). A closed-circulating system was designed to maintain up to 100 sheepshead minnows in artificial seawater for long-term exposures. Fish were maintained in this system for up to 31 weeks with weekly contaminations of pah. Due to their chemical properties significant levels of bap and mca remained in the water column for only ca. 24 Hours each week and no tumors were observed in the exposed fish during the period of the study. The incidence and types of lesions in control and exposed fish were basically similar except in catfish that were fed pah contaminated food. High levels of contamination (1mg/gm food) appeared to be toxic and lower levels of contamination (0.1 Mg/gm food) produced sufficient stress to make the catfish susceptible to fatal parasite infestations. Both species accumulated radioactively labeled pah at concentrations much higher than their normal concentrations in the water. These results demonstrate that sheepshead minnows function well as experimental organisms in artificial seawater in a closed system maintained at a noncoastal facility. Thus, they provide an excellent model system for the study of long-term effects of chronic exposure to polluting agents.

Grizzle, John M. and Paul Melius. 1982. Causes of Papillomas on Fish Exposed to Chlorinated Sewage Effluent. EPA-600/3-82-087. U.S. Environmental Protection Agency, Environmental Research Laboratory, Gulf Breeze, FL. 22 p. (Avail. from NTIS, Springfield, VA: PB83-111039)

This research was initiated to determine the cause of the oral papillomas on black bullheads (Ictalurus melas) from the final oxidation pond of the Tuskegee, Alabama, sewage treatment plant. Ames-test mutagenicity of a pond-water concentrate indicated presence of a chemical carcinogen in the pond water. However, water and sediment analysis did not identify substances suspected of causing the tumors. Cytoplasmic inclusion bodies were present in some papilloma cells, but attempts to find virions in the tumor using electron microscopy and to transmit the papillomas by injection of cell-free tumor homogenate into black bullheads were not successful. Juvenile black bullheads, yellow bullheads (Ictalurus natalis), and channel catfish (Ictalurus punctatus) were confined to cages in the oxidation pond and in a control pond. Caged fish did not develop neoplasms but most caged black bullheads in the oxidation pond developed focal oral hyperplasia and stomatitis in the same mouth locations occupied by papillomas in wild black bullheads from this pond.

Hendricks, Jerry D., Theodore R. Meyers, John L. Casteel, Joseph E. Nixon, Patricia M. Loveland and George S. Bailey. 1984. Rainbow Trout Embryos: Advantages and Limitations for Carcinogenesis Research. EPA-600/J-84-238. Natl. Cancer Inst. Monogr. 65:129-137. (ERL,GB X279).

Rainbow trout embryos are sensitive to the initiation of neoplasms in various tissues by brief exposures to solutions of water-soluble carcinogens. This characteristic was first demonstrated with the sparingly soluble liver carcinogen, aflatoxin B1 (AFB1). A 30-minute exposure of 21-day-old embryos (embryos hatch in 24-25 days at 12 degrees C) to a 0.5-ppm aqueous solution of AFB1 will result in approximately 65% of the survivors having at least 1 liver tumor, 1 year after treatment. The embryos are responsive to both AFB1 dose and the length of exposure and become increasingly sensitive with increased embryonic age. We have used rainbow trout embryos to demonstrate the hepatocarcinogenicity of other aflatoxin metabolites and precursors; aflatoxicol, aflatoxin G1, versicolorin A, and sterigmatocystin. In addition to mycotoxins, trout embryos are sensitive to several nitrosamine hepatocarcinogens including: dimethylnitrosamine, diethylnitrosamine, nitrosopyrrolidine, and 2,6-dimethylnitrosomorpholine. However, with the highly water-soluble nitrosamines, longer exposure times (up to 24 hr) are required. It is generally accepted that each of the above-named carcinogens requires metabolic activitation to the ultimate carcinogenic form. This provides indirect evidence that the trout embryo is capable of cytochrome P-450-mediated metabolism. Finally, trout embryos are sensitive to the direct-acting carcinogen, n-methyl-n'nitro-n-nitrosoguanidine. This compound produces tumors of the liver, stomach, kidney, and swim bladder, and a pronounced female-to-male sex reversal. Results to date have shown that the trout embryo is a sensitive, convenient, and economical whole animal model system with many distinct advantages for carcinogen testing and research. The major limitation has been the difficulty with exposure of the embryos to adequate doses of highly water-insoluble compounds. Alternate exposure techniques will be required for alleviation of this problem.

Schultz, R. Jack and Mary E. Schultz. 1984. Characteristics of a Fish Colony of Poeciliopsis and Its Use in Carcinogenicity Studies with 7,12-Dimethylbenz[a]anthracene and Diethylnitrosamine. EPA/600/J-84/268. Natl. Cancer Inst. Monogr. 65:5-13. (ERL,GB X311).

The viviparous fish Poeciliopsis from north-western Mexico is characterized according to its potential in cancer research. A colony of these fishes started in 1961 includes inbred strains of P. lucida (M61-9, M61-31, M61-35, and S68-4), P. monacha (S68-4 and S68-5), and P. viriosa (M65-23), which have been demonstrated by electrophoresis and tissue graft analysis to be homozygous. All-female species of hybrid origin are represented by 12 clones which, although highly heterozygous, are genetically identical or isogenic and readily accept within-clone tissue transplants. Two studies are cited in which hepatic tumors were chemically induced. In one, liver neoplasms were induced in P. lucida and P. monacha by repeated short-term exposures to an aqueous suspension of 5 ppm 7,12-dimethylbenz[a]anthracene. In the other, dose responses to the carcinogen diethylnitrosamine (DENA) were compared among 4 inbred strains, 3 hybrids from crosses between inbred strains, and 2 wild stocks of P. lucida. The incidence of hepatic tumors gradually increased from 0 to 93% depending on the concentration of the compound and the number of exposures, but no significant difference was found among the inbred strains, their hybrids, or the wild stocks. Hepatic tumors, initially induced with DENA have been successfully transplanted into the muscle tissue and abdominal cavity of members of the same strain.

Schultz, Mary E. and R. Jack Schultz. 1982. Induction of Hepatic Tumors with 7,12-Dimethylbenz(a)anthracene in Two Species of Viviparous Fishes (Genus Poeciliopsis). Environ. Res. 27(2):337-351. (ERL,GB X312).

Liver neoplasms were induced in two species of viviparous fishes Poeciliopsis lucida and P. monacha by repeated short-term exposures to an aqueous suspension of 5 ppm 7, 12-dimethylbenz(a)anthracene (DMBA). Predominantly hepatocellular neoplasms deceloped in 47 out of 106 fish surviving the period allowed for tumor development, 6-9 months after initial exposure to DMBA. The use of short-term exposure periods of 6 hours in young fish and up to 29 hours in adults reduced stress and mortalities caused by the toxicity of DMBA at 5 ppm. A lower concentration of DMBA, 0.25 ppm , failed to induce tumors in any of the surviving 230 of 295 young fish administered repeated 20-hour exposures. This study shows for the first time that DMBA is carcinogenic to fish.

Meyers, Theodore R. and Jerry D. Hendricks. 1984. Limited Epizootic of Neuroblastoma in Coho Salmon Reared in Chlorinated-Dechlorinated Water. EPA-600/J-84-003. J. Natl. Cancer Inst. 72(2):299-310. (ERL,GB X468).

During the 1976-77 brood year, approximately 12 cases of neuroblastoma were observed in a captive group of 100,000 fingerling coho salmon (Oncorhynchus kisutch) reared in a commercial hatchery. The tumors were large, occurring in the skeletal muscle near the dorsal fin causing conspicuous bulging of the overlying integument. Tumors examined from 3 fish each consisted of neuroblasts in trabecular patterns interspersed by glial fibrillar material and linear cavities resembling central neural canals lined by ependyma-like cells. Ganglion-like cells also were apparent morphologically and by special stain. Cancer of the tumor was characterized by an abundance of mitotic figures with occasional abnormal divisions, local invasion of normal tissues, and potentially metastatic tumor cell aggregates in organ vasculature. The etiology of this tumor may have been related to mutagenic-carcinogenic halogenated compounds possibly formed in the hatchery water supply during continuous chlorination of incoming river water.

Grizzle, John M. 1985. Black Bullhead: An Indicator of the Presence of Chemical Carcinogens. In: Water Chlorination: Chemistry, Environmental Impact and Health Effects, Vol. 5. EPA/600/D-86/035. Robert L. Jolley, Editor. Lewis Publishers, Chelsea, MI. Pp. 451-460. (ERL,GB X508). (Avail. from NTIS, Springfield, VA: PB86-158599)

The usefulness of exposing caged fish to polluted water to detect chemical carcinogens was demonstrated by the development of neoplasms on black bullheads. Chemical analysis in this case failed to indicate that mutagenic or carcinogenic chemicals were present, perhaps because of infrequent sampling. Laboratory exposures of black bullheads to sediment extracts (unpublished data) and brown bullhead embryos to organic extracts of the Tuskegee wastewater failed to cause tumors or other lesions that occurred on fish exposed in cages. Additional refinement of techniques may improve the usefulness of laboratory exposures; however, field exposure of caged fish is currently most satisfactory for the conditions and the carcinogen(s) present in the Tuskegee wastewater.

Hinton, David E., John A. Couch, Swee J. Teh and Lee A. Courtney. 1988. Cytological Changes During Progression of Neoplasia in Selected Fish Species. Aquat. Toxicol. 11(1,2):77-112. (ERL,GB X539).

Cytological changes during progression of hepatic neoplasia in fishes were reviewed with emphasis on recent findings in Cyprinodon variegatus and Oryzias latipes. Hepatocytes are particularly sensitive to toxic changes during early phases of response to carcinogens reflecting both lethal and sublethal alterations. Enzyme histochemical studies reveal marked deficiency of glucose-6-phosphate dehydrogenase, glucose-6-phosphatase and adenosine triphosphatase. Surviving hepatocytes are either enlarged, encircled by cells with small nuclear to cytoplasmic rations, and have altered nuclear morphology suggestive of an inability to divide, or, are smaller, apparently rapidly dividing, and have basophilic cytoplasm. In both species, development of spongiosis hepatis occurred following cytotoxic phases. This lesion apparently provides abundant space for cellular remodeling during neoplastic progression leading to eventual multinodular change. Foci of altered hepatocytes included basophilic, eosinophilic (both species) and clear cells (Cyprinodon variegatus only). Enzyme alterations preceded other morphologic alterations and were seen in cells of foci and tumors suggesting lineage of phenotypic alteration. Cytologic changes within other resident cell populations during neoplastic progression were reviewed.

Fournie, John W., William E. Hawkins, Robin M. Overstreet and William W. Walker. 1987. Exocrine Pancreatic Neoplasms Induced by Methylazoxymethanol Acetate in the Guppy, Poecilia reticulata. EPA/600/J-87/309. J. Natl. Cancer Inst. 78(4):715-725. (ERL,GB X548). (Avail. from NTIS, Springfield, VA: PB88-196266)

Exocrine pancreatic neoplasms developed in the guppy, Poecillia reticulata, following a single brief exposure to methylazoxymethanol acetate. Fish 6-10 days old were exposed to concentrations of MAM-Ac up to 100 mg/liter for 2 hours. Exposed specimens were transferred to carcinogen-free water and sampled periodically for tumor development. Pancreatic neoplasms occurred in approximately 9% of histologically examined individuals exposed to 10 mg MAM-Ac/liter or less. Neoplastic lesions were not found in 122 control specimens. The neoplasms included 6 cases diagnosed as adenoma, 7 cases diagnosed as acinar cell carcinoma, and 2 cases diagnosed as adenocarcinoma. Adenomas consisted mainly of well-differentiated acinar cells that were filled with zymogen granules. The findings of carcinogen-induced pancreatic neoplasms in guppies further strengthen the usefulness of small fish species in carcinogen testing and provide an additional model for pancreatic tumors.

Hawkins, W.E., J.W. Fournie, R.M. Overstreet and W.W. Walker. 1988. Rhabdomyosarcoma in the Japanese Medaka, Oryzias latipes (Temminck & Schlegel) and Guppy, Poecilia reticulata Peters. J. Fish Dis. 11(3):259-266. (ERL,GB X549).

Three cases of skeletal muscle neoplasms occurring in two small fish species used in carcinogen tests are reported. The cases illustrate a wide range of histologic patterns including a well-differentiated juvenile type, a well-differentiated pleomorphic type, and a poorly differentiated pleomorphic type. A rhabdomysarcoma with juvenile type features developed in the Japanese medaka, Oryzias latipes, exposed to 0.5 ml/l of the solvent dimethylformamide. Single cases of pleomorphic type rhabdomyosarcoma also occurred in the medaka and in the guppy, Poecilia reticulata, exposed to the carcinogen methylazooxymethanol acetate. These cases indicate the potential for skeletal muscle cells in medaka and guppy to become neoplastic, but the low frequency of the tumors does not necessarily establish a chemical etiology.