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Hydroxyanthraquinones as Tumor Promoters: Enhancement of Malignant Transformation of C3H Mouse Fibroblasts and Growth Stimulation of Primary Rat Hepatocytes¹

Department of Toxicology, University of Hamburg Medical School, D-2000 Hamburg 13, Federal Republic of Germany

Because danthron, though carcinogenic, does not seem to be genotoxic, it and 8 other hydroxyanthraquinones were comparatively investigated for activities associated with tumor promotion, such as stimulation of cell proliferation and enhancement of malignant transformation. The in vivo treatment of primary rat hepatocytes with danthron, aloe-emodin, chrysophanol, and rhein resulted in a 2–3-fold increase of DNA synthesis, lucidin and purpurin were less active, and emodin, purpuroxanthin, and alizarin were essentially inactive. In addition, danthron, rhein, and chrysophanol (preliminary data), but not alizarin, enhanced transformation of C3H/M2 mouse fibroblasts initiated by N-methyl-N'-nitro-N-nitrosoguanidine or 3-methylcholanthrene. The results of these in vitro studies suggest that hydroxyanthraquinones, possessing 2 hydroxy groups in the 1,8-positions, e.g., danthron, rhein, and chrysophanol, may have tumorpromoting activities. This conclusion is in accordance with the hypothesis that the in vivo carcinogenic activity of danthron may be associated with tumor promotion.

¹ Supported in part by the Deutsche Forschungsgemeinschaft (We 980/2-1) and Roggenbuckstiftung zur Krebshilfe.

² To whom requests for reprints should be addressed, at Department of Toxicology, University of Hamburg Medical School, Grindelallee 117, D-2000 Hamburg 13, Federal Republic of Germany.

Received 4/10/90. Accepted 7/13/90.