Hitherto Unknown Additive Growth Effects of Fluorene and 2-Acetylaminofluorene on Bile Duct Epithelium and Hepatocytes in Rats
The liver, more than other organs, may respond with a wide range of functional and structural lesions to xenobiotics. To identify putative tumorigenicity of a compound, its potency to cause cell proliferation is considered to be most reliable. However, most genotoxic carcinogens inhibit division of their target cells. This occurs even in the early phase after non-necrogenic doses. Contrarily, non-genotoxic carcinogens of different organotropism elevate cell proliferation in their target tissues primarily, either by restorative (post-necrotic) or by additive (chemical promoters) growth of normal and/or previously initiated cells (Clayson et al 1989). It should be noted that in man initial genotoxic events are thought to be inevitable and that cell proliferation is the main driving force in tumor development. Keeping this in mind the discovery of nongenotoxic proliferogenic factors is as important in risk assessment as that of genotoxic carcinogens (Clayson et al 1989; Butterworth 1989).
KeywordsCage Dimethyl Fluorene Diethyl Toxicology
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