SAFETY SCREENING OF DRUGS IN CANCER-THERAPY

Development of new drugs requires a thorough investigation of efficacy and safety of pharmaceuticals. The potential risks and benefits of dr ugs used in chemotherapy are carefully considered such that the benefi ts of using a new drug outweigh the risks in terms of the side effects caused by the drug. Damage to normal cells, tissues, organs and/or th e whole organism is a big concern. Several tests are now routinely per formed and are required for drug approval by various regulatory agenci es around the globe. The primary goals of such preclinical safety eval uation of drugs are: (1) to identify an initial safe starting dose and subsequent dose escalation scheme to humans; (2) to identify potentia l target organs of toxicity and reversibility of toxicity; (3) to iden tify potential damage to the genetic material (genotoxicity); and (4) to identify parameters of clinical monitoring. In this paper, various models for genotoxicity assays are presented. These include: Ames assa y, in vitro chromosome aberration assay and an in vivo micronucleus as say. New technologies, such as DNA adduct formation, DNA strand breaka ge, apoptotic changes, p53 gene expression and transgenic animal model s, are also considered.