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Sequential hepatic histologic and histochemical changes produced by diethylnitrosamine in the rhesus monkey
Journal of the National Cancer Institute
|December 1, 1976
Summary
Diethylnitrosamine exposure in rhesus monkeys induced early glycogen-rich liver cell foci. These foci are a potential precursor to neoplastic nodules and hepatocarcinomas, with further alterations indicating progression to malignancy.
Area of Science:
- Hepatology
- Toxicology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) development involves complex cellular changes.
- Understanding early pre-neoplastic lesions is crucial for cancer prevention.
Purpose of the Study:
- To investigate the early histochemical and morphological changes in the liver of rhesus monkeys exposed to diethylnitrosamine.
- To identify potential pre-neoplastic lesions and their role in hepatocarcinogenesis.
Main Methods:
- Six adult male rhesus monkeys received intraperitoneal diethylnitrosamine injections for 3-5 years.
- Monthly liver biopsies were performed and analyzed using hematoxylin and eosin staining and histochemical techniques.
- Key enzymes like glucose-6-phosphatase and ATPase were assessed.
Main Results:
- Early development of glycogen-rich hepatocyte foci was observed within 6 months.
- These foci exhibited altered enzyme activities, including decreased glucose-6-phosphatase and altered ATPase distribution.
- Neoplastic nodules and hepatocarcinomas developed in 5 out of 6 monkeys after 3-5 years, with distinct histochemical profiles.
Conclusions:
- Glycogen-rich, histochemically altered foci represent an early stage in diethylnitrosamine-induced hepatocarcinogenesis.
- Further alterations, such as loss of sinusoidal ATPase, are associated with progression towards malignancy.