Cytochrome P450-dependent alkoxyphenoxazone dealkylase activity in rat alveolar type II cells: effect of pretreatment with ß-naphthoflavone.
Rabovsky J; Judy DJ; Sapola NA; Pailes WH; McPeek M; Castranova V
Cell Biochem Funct 1989 Apr; 7(2):79-89
An improved procedure was developed for the isolation of rat alveolar type-II cells, and the properties of cytochrome-P450 dependent monoxygenase activity expressed as the O-dealkylation of four alkoxyphenoxazones (ROPh) in cells from control and beta- naphthoflavone (BNF) treated rats were examined. The specificity of the effect of BNF on P450 dependent enzyme activity was also studied. Ethoxyphenoxazone-dealkylase activity was induced 17 fold following BNF treatment and was further characterized by its kinetic parameters and sensitivities toward in-vitro inhibitors. BNF pretreatment of the rats did not result in statistically significant changes in methoxy, pentoxy, or benzyloxy phenoxazone dealkylase activity of alveolar type-II cells, although a trend towards decreased activity was noted for benzyloxyphenoxazone. Pretreatment with BNF had no effect on oxygen consumption or trypan-blue exclusion in alveolar type-II cells and macrophages, or on alveolar macrophage particle mediated superoxide release. Alveolar macrophage ethoxyphenoxazone-dealkylase and benzyloxyphenoxazone-dealkylase activities were not affected by the BNF pretreatment. The results of the study suggested that exposure to BNF resulted in an increase in type-II cell cytochrome-P450 dependent ethoxyphenoxazone- dealkylase activity but not in other alveolar type-II cell or macrophage alkoxyphenoxazone dealkylase activities or in parameters that monitor viability and cell wall integrity.
NIOSH-Author; Laboratory-animals; Alveolar-cells; Cell-damage; Cell-cultures; Enzyme-activity; Airway-resistance; Microsomal-enzymes; In-vitro-studies;
Author Keywords: Lung; type II cells; cytochrome P450; alkoxyphenoxazone dealkylase; ß-naphthoflavone
Cell Biochemistry & Function