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Biomedical subjects

J C Harshbarger

Publications and source records attributed to J C Harshbarger.

At least 19 recordsLinked to original sources
PubMed2001

MNU induction of neoplasia in a platyfish model.

Interspecific hybrid crosses between members of the fish genus Xiphophorus have been used for over 70 years to study the genetic aspects of melanoma formation. In the well-established "Gordon-Kosswig" cross, the platyfish X. maculatus is outcrossed to the swordtail X. helleri, and the resulting backcross segregants spontaneously develop melanoma. We recently produced a distinct cross between X. maculatus and another platyfish species, X. couchianus. X. maculatus strain Jp 163 A is homozygous for several X-linked pigment pattern genes, including the Spotted dorsal (Sd), Dorsal red (Dr), and Anal fin spot (Af). Af is a sex-limited trait, coding exclusively for melanophores distributed on the modified anal fin or "gonopodium" in the adult male fish. Within F1 and BC1 hybrids (to X. couchianus), the Sd pigment pattern is phenotypically suppressed, whereas Dr and Af are enhanced. We exposed BC1 hybrids to the direct-acting carcinogen N-methyl-N-nitrosourea (MNU). Treatment led to the development of schwannomas, fibrosarcomas, and retinoblastomas. In addition, numerous MNU-treated males that inherited Af developed a pronounced melanotic phenotype, with melanin-containing cells oftentimes totally covering the gonopodium and extending further to grow within the ventral regions of the fish. Genetic linkage analysis of the BC1 hybrids revealed a significant (p < 0.01) association between CDKN2X genotype and the phenotypic degree of melanization. Such an association is consistent with a locus within linkage group V playing a role in the development of melanosis and delineates three genetic preconditions and a carcinogenic scheme resulting in melanosis of the ventral regions of hybrid fish. The overall study further alludes to the potential of using Xiphophorus fish to study carcinogenic mechanisms for tumors other than melanoma (schwannoma, fibrosarcoma, and retinoblastoma) and should enable extensive pathologic and molecular genetic studies of derived neoplastic abnormalities.

Alkylating Agents↗
PubMed2001

Tumor prevalence and biomarkers of exposure in brown bullheads (Ameiurus nebulosus) from the tidal Potomac River, USA, watershed.

Associations between contaminant exposure and liver and skin tumor prevalence were evaluated in brown bullheads (Ameiurus nebulosus) from the tidal Potomac River, USA, watershed. Thirty bullheads (> or = age 3) were collected from Quantico embayment, near a Superfund site that released organochlorine contaminants; Neabsco Creek, a tributary with petroleum inputs from runoff and marinas; and Anacostia River (spring and fall), an urban tributary designated as a Chesapeake Bay region of concern, that was contaminated with polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and organochlorine pesticides. Fish were collected from the Tuckahoe River, as a reference. Cytochrome P450 activity, bile PAH metabolites, and muscle organochlorine pesticide and PCB concentrations were measured in randomly selected individuals and sediment contaminants were analyzed. We found statistically significant differences in liver tumor prevalences: Anacostia (spring), 50%; Anacostia (fall), 60%; Neabsco, 17%; Quantico, 7%; and Tuckahoe, 10%. Skin tumor prevalences were significantly different: Anacostia (spring), 37%; Anacostia (fall), 10%; Neabsco, 3%; Quantico, 3%; and Tuckahoe, 0%. Tumor prevalence in Anacostia bullheads warrants concern and was similar to those at highly contaminated sites in the Great Lakes. Evidence was found of higher PAH exposure in Anacostia fish but a cause-effect linkage could not be established. Fish tumor surveys, with histopathologic examination of internal and external organs, are recommended for monitoring the status of regions of concern.

Animals↗
PubMed2000

Ichthyophonus-like infection in wild amphibians from Québec, Canada.

Myositis associated with infection by Ichthyophonus-like organisms was diagnosed in 35 of 260 (13%) wild amphibians collected in Quebec, Canada, from 1959 to 1964 (n = 30), and 1992 to 1999 (n = 230). Infection was diagnosed in 17 green frogs Rana clamitans, 9 wood frogs R. sylvatica, 4 red-spotted newts Notophthalmus viridescens, 3 bullfrogs R. catesbeiana, 1 spring peeper Pseudacris crucifer, and 1 pickerel frog R. palustris. The spring peeper and one of the bullfrogs were collected in 1964 from the Mont Saint-Hilaire Biosphere Reserve, indicating long-term presence of the organism. Spores of the organisms invaded striated muscle fibers and were associated with variable degrees of granulomatous and eosinophilic inflammation. Infection was considered fatal in 2 green frogs, 1 wood frog, and 1 red-spotted newt. It was considered potentially significant in 3 additional green frogs in which up to 100% of the fibers of some muscles were replaced by spores associated with a severe granulomatous reaction. Ultrastructural features of Ichthyophonus-like spores included a thick trilaminated wall, a paramural cytoplasm, multiple nuclei, oval mitochondria with short tubulo-vesicular cristae and numerous ribosomes. This report represents 4 new host records and shows that ichthyophonosis is enzootic in amphibians from Quebec.

Amphibians↗
PubMed2000

Suprasellar germinoma in three lake whitefish (Coregonus clupeaformis).

Suprasellar germinomas were identified in three wild-caught lake whitefish (Coregonus clupeaformis) from the St. Lawrence River, Quebec, Canada. Histologically, the three tumors expanded the subarachnoid space of the ventral surface of the brain immediately adjacent to the pituitary gland and, in one case, infiltrated the adjacent neuropil. These tumors were characterized by nests and sheets of round cells with a high mitotic rate, separated by a scant amount of loose fibrovascular stroma. The stroma was infiltrated by a moderate number of small mononuclear cells, including rare CD3-immunoreactive lymphocytes. This is the first report of intracranial germinoma in a fish species.

Animal Diseases↗
PubMed2000

Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio).

The zebrafish (Danio rerio) has been successfully used to discover hundreds of genes involved in development and organogenesis. To address the potential of zebrafish as a cancer model, it is important to determine the susceptibility of zebrafish to tumors. Germ line mutations are most commonly induced for zebrafish mutant screens by exposing adult male zebrafish to the alkylating agent, ethylnitrosourea (ENU). To determine whether ENU induces tumors, we compared the incidence of tumors in ENU-treated fish with untreated controls. Interestingly, 18 of 18 (100%) fish mutagenized with either 2.5 or 3.0 mM ENU developed epidermal papillomas, which numbered 1 to 22 per fish, within 1 year of treatment. The induced epidermal lesions included epidermal hyperplasia, flat papillomas (0.2 to 1.2 mm), and pedunculated papillomas (1.2 to 8 mm in greatest dimension), but no skin cancers. Angiogenesis was evident in papillomas larger than approximately 1 mm. All but two papillomas contained the three cell types (keratinocytes, club, and mucous cells) of normal zebrafish epidermis; histologic variants lacked either club cells or mucous cells. Two cavernous hemangiomas and a single malignant peripheral nerve sheath tumor were also found in the treated fish. None of five untreated controls developed tumors. These studies establish the feasibility of the zebrafish as an experimental model for the study of skin tumors.

Animals↗
PubMed1999

Cutaneous mastocytomas in the neotenic caudate amphibians Ambystoma mexicanum (axolotl) and Ambystoma tigrinum (tiger salamander).

Spontaneous mastocytomas studied in 18 axolotls (Ambystoma mexicanum) and six tiger salamanders (Ambystoma tigrinum) were gray-white, uni- to multilobular cutaneous protrusions from 2 mm to 2 cm in diameter. Tumors were moderately cellular unencapsulated masses that usually infiltrated the dermis and hypodermis with the destruction of intervening tissues. Some tumors were invading superficial bundles of the underlying skeletal muscle. Tumors consisted of mitotically active cells derived from a single lineage but showing a range of differentiation. Immature cells had nearly smooth to lightly cleft or folded basophilic nuclei bordered by a band of cytoplasm with few cytoplasmic processes and containing a few small uniform eccentric granules. Mature cells had basophilic nuclei with deep clefts or folds and abundant eosinophilic cytoplasm with multiple long intertwining cytoplasmic extensions packed with metachromatic granules. The axolotls were old individuals from an inbred laboratory colony. The tiger salamanders were wild animals from a single polluted pond. They could have been old and inbred. Both groups were neotenic. These are the first mastocytomas discovered in cold-blooded animals.

Ambystoma↗
PubMed1996

Prevalence and histopathology of shell disease in turtles from Lake Blackshear, Georgia.

Turtles in Lake Blackshear, Crisp County, Georgia (USA) were evaluated for shell disease during intensive trapping efforts on 8 and 9 May 1990. The disease was most prevalent in Pseudemys concinna (74%) and Trachemys scripta (35%). The degree of necrosis on the carapace was significantly positively correlated with the degree of necrosis on the plastron in T. scripta (rs = 0.50), but not in P. concinna (rs = 0.06). Female T. scripta with lesions were significantly larger than females without lesions. Lesions were not detected on six other species of turtles. Some areas contained multinucleate osteoclasts that were destroying bone. No tumors were detected in soft tissue samples.

Analysis of Variance↗
PubMed1995

Association of prokaryotes with symptomatic appearance of withering syndrome in black abalone Haliotis cracherodii.

Withering syndrome (WS) is an epizootic fatal wasting disease that is devastating California Channel Island populations of black abalone Haliotis cracherodii. Our studies suggest a strong pathogen-disease association. The pathogen is an intracellular prokaryote that infects epithelial cells lining the gut and enzyme secreting cells of the digestive diverticula. It multiplies by binary fission in round to oval, basophilic, membrane-bound colonies teeming in the cytoplasm. Infection of the digestive diverticula is accompanied by a complete loss of digestive enzyme granules and metaplasia of enzyme secretory cells to a morphology similar to epithelium lining the gut. Extensive infection of digestive diverticular cells and the resultant deficiency in digestive enzymes correlates to the degree of pedal muscle atrophy and the severity of signs associated with WS. Electron microscopically the intracellular pathogen is a rod-shaped, ribosome-rich, gram-negative, prokaryote with a trilaminar cell wall consistent with the order Rickettsiales. Microbiological and protozoological methods produced no patterns that implicated other types of microbes. Chemical analysis of tissue from animals from a population with WS did not support an association between WS and environmental pollutant exposure to polycyclic aromatic hydrocarbons, polychlorinated biphenyls, or chlorinated pesticides.

Alphaproteobacteria↗
PubMed1995

Decline in liver neoplasms in wild brown bullhead catfish after coking plant closes and environmental PAHs plummet.

Polycyclic aromatic hydrocarbons (PAHs) in both sediment and brown bullhead catfish tissues from the Black River in Lorain County, Ohio, declined by 65% and 93%, respectively, between 1980 and 1982. Sediment PAHs declined an additional 99% by 1987, coincident with the closure of a coking facility in 1983. Contemporaneously, liver cancer in 3- to 4-year-old brown bullheads declined to about one-quarter the 1982 frequency (10% versus 39%) by 1987, while the percentage of livers without any proliferative lesions doubled (42% versus 20%). These changes were significant within age group. Our data affirm a cause-and-effect relationship between PAH exposure and liver cancer in wild fish. The data also support the efficacy of natural, unassisted remediation once the source of the pollution is eliminated.

Age Factors↗
PubMed1991

Contaminated sediments from tributaries of the Great Lakes: chemical characterization and carcinogenic effects in medaka (Oryzias latipes).

Sediments from four inshore industrial sites and a reference site in the Great Lakes were extracted with organic solvents to produce a crude extract, which was separated on alumina into two fractions: predominantly polycyclic aromatic hydrocarbons; and predominantly nitrogen-containing polycyclic aromatic compounds. Crude extracts were redissolved in acetone and analyzed by gas chromatography and gas chromatography-mass spectrometry. The acetone-redissolved crude extracts from the four industrialized sites contained 5.6-313.3 micrograms total polycyclic aromatic compounds/g sediment and 3.0-36.4 micrograms other compounds/g sediment. In addition to the typical EPA priority pollutants, a substantial amount (228.7 micrograms/g sediment) of alkyl-polycyclic-aromatic compounds was detected in sediments from one of the industrialized sites. Extracts from the reference site contained 1.55 micrograms total polycyclic aromatic compounds/g sediment. Medaka (Oryzias latipes) were exposed to multiple pulse doses of acetone-redissolved extracts and fractions. Medaka were also exposed to a known carcinogen, methylazoxymethanol acetate, to verify that chemicals produced tumors in the test fish. Acetone-redissolved extracts and fractions from contaminated sediments were toxic to medaka. Fin erosion and non-neoplastic liver abnormalities were more prevalent in medaka after exposure to acetone-redissolved extracts and fractions from contaminated sediments. Neoplasms previously associated with chemical exposure in wild fishes were induced in medaka exposed to acetone-redissolved extracts and fractions from two of the contaminated sites, but not from the reference site or controls. These findings further support the hypothesis that chemical contaminants in sediments are involved in epizootics of neoplasms in wild fishes at contaminated sites.

Animals↗
PubMed1991

Carcinogenicity of Black Rock Harbor sediment to the eastern oyster and trophic transfer of Black Rock Harbor carcinogens from the blue mussel to the winter flounder.

The eastern oyster (Crassostrea virginica) developed neoplastic disorders when experimentally exposed both in the laboratory and field to chemically contaminated sediment from Black Rock Harbor (BRH), Bridgeport, Connecticut. Neoplasia was observed in oysters after 30 and 60 days of continuous exposure in a laboratory flow-through system to a 20 mg/L suspension of BRH sediment plus postexposure periods of 0, 30, or 60 days. Composite tumor incidence was 13.6% (49 neoplasms in 40, n = 295) for both exposures. Tumor occurrence was highest in the renal excretory epithelium, followed in order by gill, gonad, gastrointestinal, heart, and embryonic neural tissue. Regression of experimental neoplasia was not observed when the stimulus was discontinued. In field experiments, gill neoplasms developed in oysters deployed in cages for 30 days at BRH and 36 days at a BRH dredge material disposal area in Central Long Island Sound, and kidney and gastrointestinal neoplasms developed in caged oysters deployed 40 days in Quincy Bay, Boston Harbor. Oysters exposed to BRH sediment in the laboratory and in the field accumulated high concentrations of polychlorinated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs), and chlorinated pesticides. Chemical analyses demonstrated high concentrations of PCBs, PAHs, chlorinated pesticides, and heavy metals in BRH sediment. Known genotoxic carcinogens, co-carcinogens, and tumor promoters were present as contaminants. The uptake of parent PAH and PCBs from BRH sediment observed in oysters also occurs in blue mussels (Mytilus edulis). Winter flounder fed BRH-contaminated blue mussels contained xenobiotic chemicals analyzed in mussels. The flounder developed renal and pancreatic neoplasms and hepatotoxic neoplastic precursor lesions, demonstrating trophic transfer of sediment-bound carcinogens up the food chain.

Animals↗
PubMed1991

Germinomas and teratoid siphon anomalies in softshell clams, Mya arenaria, environmentally exposed to herbicides.

Seminomas and dysgerminomas are epizootic in softshell clams, Mya arenaria, from three Maine estuaries contaminated with herbicides. The first epizootic was discovered in 22% of clams collected as Searsport near Long Cove Brook and three culverts that conveyed heating oil and jet fuel spilled from a tank farm in 1971. Data from subsequent epizootiological studies and a series of long-term experimental exposures of softshell clams to no. 2 fuel oil, JP-4, and JP-5 jet fuel at the U.S. EPA, Environmental Research Laboratory in Narragansett, Rhode Island, and in the field did not support an etiology by these petroleum products. In the two recent epizootics reported here, the germinomas have been observed in 3% of the softshell clams collected from Roque Bluffs near Machiasport and from 35% of softshell clams collected from Dennysville. Mya collected at Dennysville had pericardial mesotheliomas and teratoid siphon anomalies in addition to gonadal neoplasms. Estuaries at Dennysville had been contaminated by herbicides in a 1979 accidental spray overdrift during aerial application of Tordon 101 to adjacent forests. Further investigation determined widespread use of the herbicides Tordon 101, 2,4-D,2,4,5-T, and other agrochemicals in an extensive forestry and blueberry industry in both the Roque Bluffs and the Dennysville areas. Herbicide applications at Searsport were confirmed for railroad property bordering Long Cove estuary and for Long Cove Brook adjacent to the estuary where a highway department reportedly cleans its spray equipment. Herbicide contamination is the only common denominator identified at all three sites where Mya have been found with gonadal neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1990

Epizootiology of neoplasms in bony fish of North America.

Over the past 25 years, there have been an increasing number of fish tumor epizootics recognized in discrete geographical areas in North America. This is consistent with an association between tumor development in fish and exposure to waterborne contaminants as a result of increased industrialization. Reports of fish tumor epizootics from the literature, plus acquisitions at the Registry of Tumors in Lower Animals, Smithsonian Institution originate from 41 geographical regions in North America. Epizootics of hemic, neural, connective tissue, and gonial neoplasms seem unrelated to environmental pollution, but epizootics of hepatic and epidermal neoplasms appear to be caused or strongly influenced by environmental pollution. The 14 species with epizootic liver tumors are all bottom feeding fish, and tumor-bearing fish are generally located in areas where chemical contaminants are concentrated. Epidermal neoplasms are also found in fish near polluted areas, but a direct cause-and-effect link with chemical carcinogens is not clear.

Animals↗
PubMed1990

Relationship between liver tumors and age in brown bullhead populations from two Lake Erie tributaries.

We compared liver tumor frequencies, and age and length characteristics of brown bullheads (Ictalurus nebulosus) of greater than 250 mm total length from two Lake Erie tributaries. Bullheads taken from Old Woman Creek (n = 144) had no grossly observable liver tumors, while those collected in the highly industrialized Black River (n = 532) had a 30% frequency of grossly visible liver tumors during 1981-1982. Liver lesions diagnosed histologically in a randomly collected sample (n = 125) of brown bullheads from the Black River included both biliary and hepatic lesions, with cancerous neoplasms occurring in 38.4% of the fish. Black River bullheads of combined ages 4 and 5 had a significantly (p less than or equal to 0.05) greater prevalence of biliary carcinomas (35.5%) than those of ages 2 and 3 combined (18.4%). Biliary carcinoma was significantly more prevalent than hepatocellular carcinoma in age 4 fish (sexes combined) and in males of ages 3 and 4. The prevalence of hepatocellular carcinoma was significantly higher in females than in males. Age distributions of bullheads differed significantly between the two sites, while length distributions were similar. No brown bullheads of ages 6 or 7 were collected in the Black River, while these age groups composed 18% of the catch in Old Woman Creek. Brown bullheads of age 5 were almost six times more numerous in the Old Woman Creek than in Black River collections. These age and length distributions are consistent with the hypothesis that brown bullheads in the Black River were subjected to an age-selective mortality associated with high prevalences of liver carcinoma.

Aging↗
PubMed1984

Pseudoneoplasms in ectothermic animals.

Gross and cytologic similarities between certain non-neoplastic conditions and neoplasms in lower animals including fish, amphibians, and reptiles have invited misinterpretations and contested interpretations. Major categories of pseudo-neoplasms, illustrated by specific examples from material accessioned into the Registry of Tumors in Lower Animals, include infections by foreign organisms which resemble host cells (algal protothecosis and amebic pseudotumors); unusual normal conditions [giant islets of endocrine pancreas (Brockmann bodies) in liver, atypical sites of hematopoietic tissue]; nonparasitic hyperplasia (goiter, ectopic thyroid, erythroblastic proliferation suggestive of pernicious anemia, adenofibrosis); parasite-induced hyperplasia (trematode-induced fibrosis, ciliate-induced monocytic leukocytosis, trematode-induced melanosis, glochidiosis); dysmorphogenesis (teratoid anomalies); virus-induced hypertrophy (lymphocystis); and reactive lesions (metaplasia, regeneration, inflammation).

Adenocarcinoma↗