Light and electron microscopic comparisons of normal hepatocytes and neoplastec hepatocyles of well-differenciated hepatocellular carcinomas in a teleost fish

Abstract

ABSTRACT. Well-differentiated hepatocellular carcinomas (HCC's) induced in the sheepshead minnow Cyprinodon variegatus w~t h N-nitrosodiethylamine perm~tted light microscop~cal and ultrastructural comparisons of normal hepatocytes and adjacent HCC cells. Normal hepatocytes contained typical organelles with their intracellular distribution similar to that described for other teleosts. These cells revealed a strong compartmentalization of organelles consisting of restricted perinuclear cytoplasm containing rough endoplasmic reticulum (RER) and mitochondria; most of the rest of the cell's cytoplasm volume was filled with P-glycogen particles. Adjacent HCC cells at the border of the neoplasm interdigitated (invaded) between normal hepatocytes and replaced normal hepatocytes close to the HCC edge and adjacent to the bile canaliculi. Within the HCC, cells had little intercellular space between them and atypical bile canaliculi were found occasionally between adjacent hepatocytes. The HCC cells appeared to differ mainly in a quantitative, rather than in a qualitative fashion, and in the distribut~on of organelles from normal hepatocytes. HCC cells were not compartmentalized; their organelles (RER and mitochondria) were distributed throughout the cytoplasm, and only small amounts of glycogen remained diffusely distnbuted or in small masses or foci. Mitochondrial intermembrane myelin bodies (MMB's) were found frequently in the HCC cells but less frequently in the normal hepatocytes. Some cells at the edge of the HCCs appeared to be intermediate between inner HCC cells and normal hepatocytes in terms of abundance and distribution of organelles and glycogen. The possible significance of the MMB's and intermediate, edge cells is discussed, as well as the need to better characterize features of well-differentiated hepatic neoplasms in order to assure their proper inclusion in neoplasm incidence/prevalence data in fish carcinogenesis assays and field studies.

Novel protective role of curcumin and taurine combination against experimental hepatocarcinogenesis

“…Furthermore, electron microscopy confirmed the histopathological changes and showed the presence of HCC in the DENA-treated group, as indicated by mitochondrial accumulation, RER stacks and nuclear malignant changes. These results were consistent with a previous study, which demonstrated that normal hepatocytes had fewer mitochondria as compared with HCC cells (66). In addition, HCC cells were shown to contain a greater abundance of, and more widely dispersed, RER.…”

Comparative Histological Study of Teleost Livers in Relation to Phylogeny

“…In teleost livers, a large number of morphological studies of the hepatic cells, hepatocytes (Langer, 1979;Nopanitaya et al ., 1979b), endothelial cells (Ferri and Sesso, 1981;Sato and Yamamoto, 1983), hepatic stellate cells (Nopanitaya et al ., 1979b;Eastman and De Vries, 1981), Kupffer cells (Hampton et al ., 1987;Rocha et al ., 1997) and bile ductules cells (Shin, 1978;Tanuma, 1980;Satoh, 1983), in the hepatic lobule, and the biliary system (Hampton et al ., 1985; and innervation (Esteban et al ., 1998), have revealed details of their connection (Sakano and Fujita, 1982;Hampton et al ., 1989;Speilberg et al ., 1994), and established the liver structures and functions (Motta, 1984). The recent aims have been as follows: (1) ecological and toxicological studies of the liver as a biomarker of environmental pollution (Braunbeck, 1994), (2) a histochemical study to establish whether the liver has a central role in metabolism (Orbea et al ., 1999;Jung et al ., 2002), (3) a pathological study of the liver as an important organ for the analysis of fish diseases (e.g., cholestasis and neoplasm) (Couch, 1991;1993;Okihiro and Hinton, 2000). From current zoological viewpoints, the themes of biodiversity or evolution have been focused and investigated (Gemballa et al ., 2003), but there has been little phylogenic research (Satoh, 1983;Cornelius, 1985;Akiyoshi et al ., 2001) in any vertebrates into the evolution of the liver.…”

Effects of mixtures containing different protein and fatlevels on growth and feed conversion ratio of common carp (Cyprinus carpio,L., 1758)

“…Tako je, i u izvedenom eksperimentu sa razliĉitim nivoima masti nabubrelost hepatocita, verovatno posledica intenzivne ishrane i procentualnog uĉešća masti u hrani. Vakuolizacija hepatocita se dogaĊa zbog morfoloških promena u citoplazmi i kompartmentacije preraspodele organela i vakuola u citoplazmi, usled ĉega se organele uglavnom nalaze u uskom krugu oko jedra, a u vakuolama koje nastaju se gomilaju rezervne materije, glikogen i/ili lipidi (Couch, 1993). Nalaz koji ukazuje na ekscentriĉnost jedara usled velikih vakuola, podudara se sa Caballero et al (1999) koji sliĉna ekscentriĉna jedra nalaze u ispitivanju jetre Sparus aurata zavisno od nivoa lipida i kvaliteta ribljeg brašna.…”