The use of isolated rat hepatocytes to measure unscheduled DNA synthesis as a screen for chemical carcinogens

Abstract

Isolated rat hepatocytes are being used in a variety of ways to answer fundamental questions concerning the metabolism of chemical compounds. These cells retain a high capacity to metabolise xenobiotics when treated shortly after isolation, as either suspensions or after attachment. The advantage of intact cells over rat liver enzyme preparations such as post-mitochondrial supernatant in assessing the likely in vivo metabolic fate of xenobiotics are numerous. When unscheduled DNA synthesis (UDS) induced in these cells is used as an endpoint to detect electrophile generation by carcinogens, again important questions concerning the extent and route of activation can be answered. However, the detection of UDS in these cells has been suggested as a possible screen for the detection of chemical carcinogens. It is the very advantage of the system in approaching the true in vivo situation that may work against its usefulness as such a screen by reducing its sensitivity.