Ward J M, Diwan B A, Lubet R A, Henneman J R, Devor D E
Tumor Pathology and Pathogenesis Section, National Cancer Institute, Frederick, MD.
Prog Clin Biol Res. 1990;331:85-108.
Mouse liver tumors are important end points for safety assessment of chemicals in rodent carcinogenicity assays. The mechanisms of induction of these tumors, whether by chemicals with significant genotoxic activities or by chemicals without such activities, remain unknown. If test mice have spontaneous tumors of high or low background incidence, the promotion of these tumors or of spontaneously initiated or susceptible cells may provide a basis for carcinogenesis induced by these compounds. Likewise, chronic toxicity and its associated target cell hyperplasia may also lead to promotion of these tumors. Experimental systems have been developed to study the mechanisms of tumor promotion in mouse liver. These models should significantly advance research into mechanisms of hepatocarcinogenesis and tumor promotion in mouse liver and may subsequently be used for human risk assessment.
小鼠肝脏肿瘤是啮齿类动物致癌性试验中化学物质安全性评估的重要终点。这些肿瘤的诱发机制,无论是由具有显著基因毒性活性的化学物质引起,还是由不具有此类活性的化学物质引起,仍然未知。如果试验小鼠有高背景发病率或低背景发病率的自发性肿瘤,这些肿瘤或自发启动或易感细胞的促进作用可能为这些化合物诱导的致癌作用提供基础。同样,慢性毒性及其相关的靶细胞增生也可能导致这些肿瘤的促进。已经开发了实验系统来研究小鼠肝脏中肿瘤促进的机制。这些模型应该能显著推进对小鼠肝脏肝癌发生和肿瘤促进机制的研究,随后可用于人类风险评估。