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Review: Exploring anticarcinogenic agents in a rat hepatocarcinogenesis model--focus on selenium and statins
Linda Björkhem-Bergman1, Lena Ekström, Lennart C Eriksson
1Division of Clinical Pharmacology C1-68, Department of Laboratory Medicine, Karolinska University Hospital, Huddinge, Karolinska Institute, 141 86, Stockholm, Sweden. linda.bjorkhem-bergman@karolinska.se
Abstract:
In this review, we describe a rat model for chemically induced hepatocarcinogenesis that can be used for studying the anticarcinogenic effects of different agents. In this model the process of carcinogenesis can be followed through the different stages of initiation, promotion and progression. Mechanistic studies of anticarcinogenic agents can be carried out and two examples are given by studies on selenium and statins as anticarcinogenic agents. These compounds suppress cancer via different mechanisms. In the case of selenium the induction of glutathione peroxidase 4 and inhibition of lipid peroxidation might be a part of the anticarcinogenic effect. In the case of statins, the inhibition of ubiquinone synthesis, as well as of the selenium-containing enzyme thioredoxin reductase 1 (TrxR1) might explain their anticarcinogenic properties. Interestingly, also in the case of selenium the inhibited carcinogenesis was associated with reduced TrxR activity, indicating an important role for this enzyme in carcinogenesis.