Minimal Neoplasias in Experimental Liver Carcinogenesis
The rodent liver provides a unique opportunity to study the early stages of chemical carcinogenesis. If a rat or a mouse is exposed for a long period to a hepatocarcinogen, hepatocellular carcinomas develop which invade and replace part of the normal liver, and sometimes tumor cells disseminate to give rise to lung metastasis. Long before this final stage is reached cellular changes can be observed in the liver parenchyma. Foci of altered hepatocytes appear which show an aberration from the enzymatic pattern of normal hepatocytes. These foci can best be demonstrated in enzyme histochemical preparations in cryostat sections prepared from the liver at early stages of carcinogen exposure. Small islands of hepatocytes are then seen which show a deficiency of glucose-6-phosphatase as described in a preliminary report first in 1964 by the Friedrich-Freksa group (Gössner and Friedrich-Freksa 1964). In the same year, Bannasch and Müller reported that during hepatocarcinogenesis foci of glycogen-storing cells can be observed and they related their occurrence to the previous exposure to a hepatocarcinogen. Interestingly, it was in 1961 that Grundmann pointed out that basophilic foci occur in the liver after carcinogen exposure and he suggested that these subpopulations in the liver might represent precursor lesions in hepatocarcinogenesis.
KeywordsPartial Hepatectomy Liver Carcinogenesis Carcinogen Exposure Tumorigenic Cell Line Initiation Sensitivity
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