Liver Carcinogenesis by Diethylnitrosamine in the Rat

Abstract

Diethylnitrosamine was continuously administered to rats at a dose rate of low toxicity. Ninety-two percent of the animals died with multicentrical hepatocellular carcinomata within a narrow and highly reproducible time interval. Discontinuing the carcinogen during the experiment resulted in a prolonged median time until death, a reduced tumor yield, and a lessened slope of the dose-response curve. Partial hepatectomy after discontinuation of the drug did not change either tumor yield or time of death. The obtained dose-response relationships support the concept that carcinogenic effects of single doses are irreversible and cumulative. Daily, low-dose, total-body x-irradiation had no significant effect on the response of rat liver to the carcinogen.

A blood–tumor barrier limits gene transfer to experimental liver cancer: the effect of vasoactive compounds

“…A model closer to the human situation is the induction of HCC with carcinogens such as diethylnitrosoamine (DENA) which causes the development of HCC through different steps with formation of preneoplastic foci, neoplastic nodules and eventually HCC nodules of different size. [13][14][15] In previous reports we and others have shown that in this animal model, gene transfer to large tumor nodules was very low by intraportal administration of adenoviral vectors. 7,16,17 Since primary liver tumors receive blood supply mainly from the hepatic artery, 18 some authors have compared the intraportal and intra-arterial route for vector administration in DENAinduced HCC.…”

Long-Term Radioiodine Retention and Regression of Liver Cancer after Sodium Iodide Symporter Gene Transfer in Wistar Rats

“…Experiments were performed under the institutional and European Union guidelines for laboratory animal care. Hepatocarcinoma was induced in 6-week-old male Wistar rats weighing 150 -180 g by the daily intake of diethylnitrosamine (Sigma-Aldrich, St. Louis, MO) in their drinking water (100 mg/L) for 8 weeks (27). The rats had received thyroxin (T4) supplementation (50 g/L) in their drinking water to reduce unwanted thyroid iodine uptake.…”

Hippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis

“…Abnormal activation of the Wnt/β-catenin pathway causes many types of tumors in humans including hepatoblastoma and HCC (27). In mice, hepatocyte-specific expression of active β-catenin resulted in hepatomegaly and HCC development when induced by the chemical carcinogen diethylnitrosamine (DEN) (27)(28)(29)(30), and DEN injection is required in many genetic liver tumor models (1,31). Importantly, HCC forms in 100% of Mst1/2 double-mutant mouse livers by the age of 4 months, without chemical induction, while 50% of transgenic mice overexpressing TGF-α or E2F1 develop HCCs when older than 12 months (32,33).…”