Towards a better understanding of early drug-induced regulatory mechanisms of liver tumorigenesis (original) (raw)

Abstract

Non-genotoxic carcinogens (NGC) form a group of molecules that do not directly bind DNA (1) but that produce perturbations in the gene expression and epigenetic state of cells which facilitate tumor formation, typically through the promotion of preexisting neoplastic cells into neoplasms. The molecular events underlying the NGC-induced transformation of normal hepatocytes to altered hepatocellular foci are still unclear and no acute early molecular markers for NGC are available for drugs under development. According to regulatory expectations, drug safety is tested in both short term in vitro and long-term in vivo studies in several experimental animals (rodent and non-rodent species) prior testing on human. As the safety assessment in experimental animals has been very successful in predicting toxicity of biologically active chemicals in humans, differences in species biochemistry or pathophysiology be- tween human and rodents have raised doubts regarding the appropriateness of ext...

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