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Morphometry of Hepatic Neoplasms and Altered Foci in the Mummichog, Fundulus heteroclitus

University of Maryland College Park, Department of Veterinary Medicine, Aquatic Pathobiology Laboratory, College Park, Maryland, USA

David L. Smith

University of Maryland School of Medicine, Department of Epidemiology and Preventive Medicine, Baltimore, Maryland, USA

Wolfgang K. Vogelbein

Virginia Institute of Marine Science, College of William & Mary, Gloucester Point, Virginia, USA

John C. Harshbarger

Department of Pathology, George Washington University Medical Center, Washington, DC, USA

Prabhakar R. Gudla

University of Maryland College Park, Department of Biological Resources Engineering, College Park, Maryland, USA

Michael M. Lipsky

University of Maryland School of Medicine, Department of Pathology, Baltimore, Maryland, USA

Andrew S. Kane

University of Maryland College Park, Department of Veterinary Medicine, Aquatic Pathobiology Laboratory, College Park, Maryland, USA, akane{at}umaryland.edu

The goal of this study was to intensively sample a small number of livers from a population of mummichog exposed to PAH-contaminated sediments and evaluate them for lesion pathology, distribution, shape, and volume, and the number of histological sections needed to adequately describe the extent of various lesions. Volumetric data for each lesion type from each step section was derived from digitized section images. The total number of hepatic alterations ranged from 10—125 per fish. Alterations included: eosinophilic, basophilic, and clear cell foci; hepatocellular carcinomas; hemangiopericytomas; and cholangiomas. Lesion volumes ranged from 0.00012—64 mm3 and represented 0.21%—67% of total liver volume. There was a tendency for the lesions to be more dorsal-ventrally compressed than spherical or ropelike when observed from longitudinal sections. Periodic subsampling of the data indicated that, on average, 6 evenly spaced, longitudinal histological sections were required to accurately estimate lesion volume and extent in our model population. These data provide a formulation for histological sampling techniques and methodological support for piscine and other cancer study models that observe lesion volume changes over time. Further, this study fosters the development of early quantitative endpoints, rather than using a large number of animals and waiting for tumor progression or death to occur.

Key Words: Cancer • mummichog • lesion volume • liver • morphometry • neoplasia • PAH (polycyclic aromatic hydrocarbons) • stereology.

References

• Boorman, G.A., Botts, S., Bunton, T.E., Fournie, J.W., Harshbarger, J.C., Hawkins, W.E., Hinton, D.E., Jokinen, M.P., Okihiro, M.S., and Wolfe, M.J. (1997). Diagnostic criteria for degenerative, inflammatory, proliferative nonneoplastic and neoplastic liver lesions in medaka (Oryzias latipes): Consensus of a National Toxicology Program Pathology Working Group. Toxicol Pathol 25, 202—10.[Abstract/Free Full Text]
• Charleston, L.B., Thyer, A.C., Klein, N.A., Soules, M.R., and Charleston, J.S. (2003). An improved method for the production of slides from oversized samples of glycol methacrylate-embedded tissues: application for optical dissector based stereology. J Histotechnol 26, 49—52.[Web of Science]
• Cooke, J.B., and Hinton, D.E. (1999). Promotion of 17ß-estradiol and ß—hexachlorocyclohexane of hepatocellular tumors in medaka, Oryzias latipes. Aquat Toxicol 45, 127—45.[Medline] [Order article via Infotrieve]
• Coward, K., and Bromage, N.R. (2001). Stereological validation of ovarian biopsy as a means of investigating ovarian condition in broodstock tilapia in vivo. Aquaculture 195, 183—8.[CrossRef][Web of Science]
• Eustis, S.L., Hailey, J.R., Boorman, G.A., and Haseman, J.K. (1994). The utility of multiple-section sampling in the histopathological evaluation of the kidney for carcinogenicity studies. Toxicol Pathol 22, 457—72.[Abstract/Free Full Text]
• Hanigan, M.H., Winkler, M.L., and Drinkwater, N.R. (1993). Induction of three histochemically distinct populations of hepatic foci in C57BL/6J mice. Carcinogenesis 14, 1035—40.[Abstract/Free Full Text]
• Hinton, D.E., and Couch, J.A. (1998). Architectural pattern, tissues and cellular morphology in livers of fishes: relationship to experimentally-induced neoplastic responses. In: Fish Ecotoxicology, T. Braunbeck, D. E. Hinton, and B. Streit (eds). Birkhauser Verlag, Basel, Switzerland, pp. 141—64.
• Kane, A. S., Ed. (1996). Fish Guts: A Multimedia Guide to the Art and Science of Fish Anatomy, Health, and Necropsy. APC Press, Baltimore, MD.
• Lawrence, M.C. (1992). Least-squares method of alignment using markers. In: J. Frank, editor, Electron Tomography: Three-Dimensional Imaging with the Transmission Electron Microscope, Plenum Press, New York, pp. 197— 204.
• Mazonakis, M., Damilakis, J., Maris, T., Prassopoulos, P., and Gourtsoyiannis, N. (2002). Comparison of two volumetric techniques for estimating liver volume using magnetic resonance imaging. J Magn Reson Imaging 15, 557—63.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pitot, H.C., Goldsworthy, T., Campbell, H.A., and Poland, A. (1980). Quantitative evaluation of the promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin of hepatocarcinogenesis from diethylnitrosamine. Cancer Res 40, 3616— 20.
• Profet, E.B., Mills, B., Arrington, J.B., and Sobin, L.H. (1992). Laboratory Methods in Histotechnology. Armed Forces Institute of Pathology, Registry of Pathology, Washington, DC.
• Pugh, T.D., King, J.H., Koen, H., Nychka, D., Chover, J., Wahba, G., He, Y., and Goldfarb, S. (1983). Reliable stereological method for estimating the number of microscopic hepatocellular foci from their transactions. Cancer Res 43, 1261—8.[Abstract/Free Full Text]
• Stevens, J.K., and Trogadis, J. (1984). Computer-assisted reconstruction from serial electron micrographs: a tool for the systematic study of neuronal form and function. Ad Cell Neurobiol 5, 341—69.
• Stine, C.B. (2001). Morphometric evaluation of hepatic lesions in killifish, Fundulus heteroclitus, exposed to polycyclic aromatic hydrocarbons. Masters Thesis, University of Maryland at Baltimore.
• Umeyama, S. (1991). Least-squares estimation of transformation parameters between two point patterns. IEEE Trans Pattern Anal Machine Intel 13, 376—80.[CrossRef]
• Vogelbein, W.K., Fournie, J.W., Van Veld, P.A., and Huggett, R.J. (1990). Hepatic neoplasms in the mummichog Fundulus heteroclitus from a creosote-contaminated site. Cancer Res 50, 5978—86.[Abstract/Free Full Text]
• West, M.J. (1993). New stereological methods for counting neurons. Neurobiol Aging 14, 275—85.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Xu, Y.H., Campbell, H.A., Sattler, G.L., Hendrich, S., Maronpot, R., Sato, K., and Pitot, H.C. (1990). Quantitative stereological analysis of the effects of age and sex on multistage hepatocarcinogenesis in the rat by use of four cytochemical markers. Cancer Res 50, 472—9.[Abstract/Free Full Text]

Toxicologic Pathology, Vol. 32, No. 4, 375-383 (2004)
DOI: 10.1080/01926230490440899


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Stine, C. B. Articles by Kane, A. S. Search for Related Content PubMed PubMed Citation Articles by Stine, C. B. Articles by Kane, A. S. Social Bookmarking                         What's this?