Induction of cytochrome P-450IA1 activity in response to sublethal stresses in microcarrier-attached Hep G2 cells

Abstract

Cell damage for cells grown on microcarriers in suspension is a critical problem for scale-up of microcarrier reactors. In order to study cell damage as a mechanistic process, a cellular response that is more sensitive than changes in growth and death rates and would be more closely related to cell regulatory mechanisms would be advantageous. We have observed the induction of a specific cytochrome P-450 monooxygenase, P-450IA1 (CYP1A1), to be a sensitive method for assessing the response of microcarrier-attached Hep G2 cells to stress resulting from hydrodynamic shear and oxygen deprivation. The kinetics of induction and amount of CYP1A1 formed in response to subtle shear stress, moderate shear, and hypoxia are described. Increased stress results in increased CYP1A1 formation.