Effect of caloric restriction on the induction of hepatic cytochrome P-450 and Ah receptor binding in C57BL/6N and DBA/2J mice

Abstract

While it is known that caloric restriction alters activities of certain xenobiotic metabolizing enzymes, the mechanism(s) by which this occurs have not been determined. In this study, caloric restriction (CR) increases activities of liver cytochrome P450IA1 dependent ethoxyresorufin-O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) and cytochrome P450IIB1 dependent pentoxyresorufin-O- dealkylase (PROD) in DBA/2J or C57BL/6N mice. However, the cytosolic Ah receptor binding in both strains of mice was not increased. The hepatic cytochrome P450IA1 activity was increased by CR in DBA/2J mice (a strain lacking normal Ah receptor binding), indicating that this induction need not be mediated by the Ah receptor. The effects of CR, sex and strain on P450IA1 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were also determined. Specific induction of cytochrome P450IA1 by TCDD was greater in females than in males of both strains, whereas the P450 isozymes induced in male DBA/2J mice had less specificity toward 7-ethoxyresorufin than those induced in C57BL/6N mice. Moreover, P450IA1 induction by TCDD was significantly potentiated by CR in the DBA/2 strain, indicating the interactive involvement of different regulatory mechanisms.