Probing the control elements of the CYP1A1 switching module in H4IIE hepatoma cells.

Previous research from our laboratory has shown a switch-like response to PCB 126 mediated CYP1A1 induction in primary rat hepatocytes and in H4IIE rat hepatoma cells. On a single cell level, cells appear to be either "on" or "off" for CYP1A1 induction at a given dose; some cells never respond to PCB 126. These cells represent a non-responding population.

Regional induction of CYP1A1 in rat liver following treatment with mixtures of PCB 126 and PCB 153.

Liver enzyme induction has been shown previously to be regional with clear borders between induced and uninduced regions in vivo, and cells either fully induced or not induced in vitro. The current study examined this phenomenon in vivo by evaluating enzyme induction after exposure to PCB 126 and PCB 153 in female Fisher 344 (F344) and male Sprague-Dawley (SD) rats. IHC revealed a regional induction of CYP1A1 after exposure to PCB 126, apparent in the centrilobular region at lower doses and progressing to panlobular with higher doses.

Induction of CYP1A1 in primary rat hepatocytes by 3,3',4,4',5-pentachlorobiphenyl: evidence for a switch circuit element.

In vivo induction of CYP1A1 in hepatocytes by aryl hydrocarbon receptor agonists is heterogeneous. Using immunohistochemistry, cells appear to be either induced or not induced as if the response of an individual cell is better represented as a switch. We have examined induction of CYP1A1 in vitro in primary rat hepatocytes to distinguish the responses of populations of cells and responses of individual cells.

Single cell analysis of switch-like induction of CYP1A1 in liver cell lines.

The shape of the dose-response curve may vary depending on whether one examines response at a population or a single cell level. Populations of cells may exhibit a graded response whereas single cell responses may have threshold or switch-like behavior. Studies in vivo and in vitro using primary hepatocyte cultures have shown that induction of CYP1A1 in the liver exhibits switch-like behavior in response to PCB 126 (3,3',4,4',5-pentachlorobiphenyl).