The Anatomic Pathology Evaluation of Liver with Diethylinitrosamine Treated via Intraperitoneal Injection Singly and Peros for 90 Days Carcinogenicity Study in F344 Rats

Objective：To establish the integrity experiment method of short（ medium）- term carcinogenicity test pursuant to GLP, make into relative SOP and improve the safeguard in the center. Methods：Diethylinitrosamine（DEN） is known as carcinogenic agent, whose target organ is liver. Using the two-stage carcinogenesis test method, DEN was treated to F344 rats via intraperitoneal injection singly（200 mg/kg） , and peros administrated for 90 days（10 ppm）. The liver in any group rat will be examined by light microscopy. Results：In pathologic examination, no liver cell tumor was shown in the livers of the rats that were singly treated with a carcinogenic chemical-DEN. Foci of cellular alteration were observed in the livers of these rats. The proliferation lesions of liver from slight to seveity （foci of cellular aherationepatocelluar adenoma-hepatocellular carcinoma） were observed in the livers of the rats which exposed peros to a low dose of DEN for 90 days after initiation by a single intraperitoneal injection. The incidence of hepatocelluar tumor was 35% in male animal ,which was not shown in the liver of female rat. Conclusion：For current results, it may be possible that low-dose DEN acts as a promotor of hepatocelluar tumor if it was exposed in a population for a long time. It is considered that male hormone has a synergistic effect on hepatocelluar tumor development of DEN. This two-stage carcinogenesis test might be a new model for the study of drug induced and promoted carcinogenesis, which could be used to evaluate the carcinogenesis of chemical compound fast.