PUBLICATION

Cytological alterations in fish hepatocytes following in vivo and in vitro sublethal exposure to xenobiotics — structural biomarkers of environmental contamination

Authors
Braunbeck, T.
ID
ZDB-PUB-131205-3
Date
1998
Source
Fish Ecotoxicology   86: 61-140 (Chapter)
Registered Authors
Braunbeck, Thomas
Keywords
none
MeSH Terms
none
PubMed
none Full text @ Fish Ecotoxicology
Abstract

Cytopathological alterations in hepatocytes of fish following exposure to xenobiotic compounds represent a powerful tool to reveal sublethal effects of chemicals and to elucidate underlying modes of action. The present communication reviews the available information about ultrastructural changes in fish liver as well as isolated hepatocytes; whereas the discussion of in vivo effects is primarily focused on data from rainbow trout (Oncorhynchus mykiss) and zebrafish (Danio rerio), the presentation of in vitro data has been restricted to results from experiments with rainbow trout hepatocytes due to a lack of data from studies with hepatocytes from other species. Both in vivo and in vitro exposure to xenobiotics results in sensitive, selective, and, especially in in vitro experiments, extremely rapid responses of hepatocytes, which, however, may be confounded by internal parameters (species, sex, age, hormonal status) and external parameters (temperature, nutrition, duration of exposure). Thus, transfer of results and conclusions from one experiment to another is usually not possible. Likewise, in vitro results may not necessarily be extrapolated to the situation in intact fish, and effects by acute toxic exposure cannot be translated into sublethal effects.

Hepatocellular reactions consist of both unspecific and substance-specific effects; in any case, as a syndrome, the complex of all changes induced by a given xenobiotic, is specific. Especially in the lower exposure range, most, if not all, ultrastructural alterations appear to be fully reversible; upon cessation of exposure, restitution of hepatocellular integrity is usually accomplished within a few days. Most early reactions of hepatocytes apparently serve functions within the general adaptation syndrome, which is induced to compensate for the misbalance in organismic homeostasis. Most ultrastructural alterations after sublethal exposure have, therefore, to be classified as indicators of adaptive processes and may be contrasted to irreversible, i.e., degenerative and truly pathological phenomena. These adaptive processes should, by definition, not have consequences at higher levels of biological organization; yet, as biomarkers, they are of ecotoxicological relevance. Thus, with regard to their (eco)toxicological significance, components of this nonspecific “general toxicant adaptation syndrome” may serve as early and sensitive warning signals of chemical exposure, whereas more specific changes may be of advanced diagnostic value and may serve as indices for the identification of xenobiotics.

Integration of cytopathological alterations into routine aquatic toxicology requires quantification by means of stereological techniques, which make structural data accessible for statistical analysis and comparable with quantitative techniques such as biochemistry and molecular biological methods. Implementation of cytopathological techniques into routine long-term investigations with fish gives credit to the principles of animal welfare and protection, since more-in-depth analysis of internal mechanisms of sublethal chemical contamination in addition to the study of externally overt symptoms of intoxication adds to a refinement of fish experiments. One step further towards reduction of animal experiments may be achieved by translation of environmental cytopathology to primary hepatocyte cell cultures.

Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping