DEN+2-AAF-induced multistep hepatotumorigenesis in Wistar rats: supportive evidence and insights

Diethylnitrosamine (DEN), found in many commonly consumed foods, has been reported to induce cancers in animals and humans. Several models have been developed to study multistage carcinogenesis in rat liver; these include the Solt–Farber-resistant hepatocyte model. In the Solt–Farber model, the init...

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Bibliographic Details
Published in:Protoplasma 2013-02, Vol.250 (1), p.175-183
Main Authors: Malik, Shabnam, Bhatnagar, Shilpa, Chaudhary, Naveen, Katare, Deepshikha Pande, Jain, S. K.
Format: Article
Language:English
Subjects:
2-Acetylaminofluorene - toxicity
Animals
Biomedical and Life Sciences
Carcinogenesis - chemically induced
Carcinogenesis - metabolism
Cell Biology
Diethylnitrosamine - toxicity
Disease Models, Animal
Life Sciences
Lipid Peroxidation - drug effects
Liver - drug effects
Liver - pathology
Liver Neoplasms, Experimental - chemically induced
Liver Neoplasms, Experimental - enzymology
Liver Neoplasms, Experimental - metabolism
Liver Neoplasms, Experimental - pathology
Male
Original Article
Plant Sciences
Random Allocation
Rats
Rats, Wistar
Zoology
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Summary:Diethylnitrosamine (DEN), found in many commonly consumed foods, has been reported to induce cancers in animals and humans. Several models have been developed to study multistage carcinogenesis in rat liver; these include the Solt–Farber-resistant hepatocyte model. In the Solt–Farber model, the initiation consists of either a necrogenic dose of a hepatocarcinogen or a non-necrogenic dose in conjunction with partial hepatectomy (PH). We report a novel protocol for tumor induction in liver which eliminates the need for PH. Male Wistar rats were injected with single i.p. dose of DEN (200 mg/kg body weight), controls received saline only. After 1 week of recovery, the DEN-treated animals were administered with the repeated doses of 2-acetyamino fluorine (150 mg/kg body weight) orally in 1 % carboxymethyl cellulose that served as promoting agent. Thirty days after the DEN administration, hepatocellular damage was observed as evident by histopathological analysis. The marker enzyme analysis showed elevated levels of serum AST, ALT, and alkaline phosphatase and a decrease in the levels of liver superoxide dismutase and catalase. The oxidative stress in liver was confirmed by elevated levels of lipid peroxidation and a decrease in antioxidant parameters.
ISSN:0033-183X
1615-6102
DOI:10.1007/s00709-012-0392-8