Effect of diallyl sulfide on tetrachlorodibenzo-P dioxin-induced cytochrome P-450 1a1 gene in mouse lung

Abstract

Cytochrome P-450 (CYP) 1A1 plays a key role in the metabolic activation of procarcinogen, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The present study was conducted to investigate inhibitory effect of diallyl sulfide and garlic extract on CYP1A1 induced by TCDD in mouse lung. CYP1A1 was induced by a single oral gavage of TCDD (100 ng/kg) to mouse and the induction was confirmed by the increase of its enzyme activity and of immunoprecipitable protein as well as that of mRNA for CYP1A1. When dially sulfide (200 mg/kg) or garlic extract (50 mg/kg) were given 4 days prior to TCDD administration, CYP1A1 activity measured by benzo(a)pyrene hydroxylase or 7-ethoxyresorufin-O-deethylase and the expression detected by Northern blot analysis using CYP1A1 cDNA decreased significantly in the lung compared to the TCDD-induced activities. On the other hand, those activities in the liver decreased moderately, indicating tissue specificity of the CYP gene expression. These results together with poor correlation of CYP1A2 activity under the same experimental condition indicate that the reduction of CYP1A1 gene expression by diallyl sulfide or garlic extract is selective in mouse lung induced by TCDD.