Establishment of a liver cancer model induced by DENA in Sprague-Dawley rats / 中华放射学杂志

ABSTRACT

Objective To explore the feasible approach for establishment of a liver cancer model induced by N-nitrosodiethylamine(DENA)with Sprague-Dawley rat,and to provide ideal animal model for imaging diagnosis and interventional therapy.Methods One-hundred and forty male SD rats were administrated with 0.95 g/L DENA for 10 weeks,and MRI was performed for inspecting pathological changes of rat livers on the following week.When the liver tumor was proved then the rat will be the candidate for sequential procedures,otherwise the animal continued under observation until next MRI examination after 4 weeks.DSA was done in 64 rats'for detecting blood supply of liver tumors.Animals were sacrificed with an overdose of chloral hydrate,The representative tumor tissues were fixed in 10% formalin and 2.5% glutaraldehyde for light and electron microscopy analysis respectively.Alpha fetoprotein(AFP) and hepatocyte were assaied by immunohistochemistry technique in order to identify intrinsic trait of the harvested tumors.Results The earliest induced tumor was detected on 11th week and the latest was on 20th week by MRI,and the median period was 13.9 weeks.Tumor size ranged from 2 mm to 40 mm in diameter. The rate of single and multi-induced tumor was 9.7%(7/72)and 90.3%(65/72),respectively.87.7% (57/65)" of the induced multiple tumors was with hepatocirrhosis and 18.1% of these tumors combined with extrahepatic neoplasm or metastasis.Plenty blood supply was proved by DSA in most of those tumors. Tumors not only derived from hepatocyte but also manifested positive expression of AFP.Histological types of these tumors include hepatocellular carcinoma(HCC)(92.0%,66/72),intrahepatic cholangiocarcinoma (ICC)(4.0%,3/72),and combined HCC and ICC(4.0%,3/72),respectively.Electro-microscope analysis indicated that cytoplasm and organelle of induced tumors were abnormal distinctly compared with those of non-carcinomatous cells.Conclusion DENA can induce ideal rat liver cancer as a feasible animal model,MRI is the best approach for scrutinizing pathological changes of rat livers during induced period.