The expression of cytochrome P450 genes directly within target cells is an important determinant of human susceptibility to cancers and other chemically initiated diseases. One pivotal gene, C Y P 1 A 1 codes for an inducible cytochrome P450 isozyme 1A1 responsible for the bioactivation of numerous carcinogenic polycyclic hydrocarbons. In the present study, the effects of 3-methylcholanthrene, a polycyclic aromatic hydrocarbon, on the activity and expression of CYP1A1 and the protective effects of diallyl sulfide on 3-methylcholanthrene-induced changes in mice liver and lung were investigated. After a four daily 3-methylcholanthrene-treatment (25 mg/kg, i.p.), liver and lung microsomal 7-ethoxyresorufin-Odeethylase (EROD) activity, associated with CYP1A1, was increased. A corresponding increase in the level of CYP1A1 mRNA was observed in mouse liver and lung after 3-methylcholanthrenetreatment by Northern blot analysis. Diallyl sulfide reduced 3-methylcholanthrene-induced CYP1A1 mRNA expression and its associated EROD activity in mouse liver and lung. The modulation of CYP1A1 mRNA by 3-methylcholanthrene and diallyl sulfide was mainly due to transcriptional regulation.
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Hong, YS., Park, HY. & Park, SS. Diallyl sulfide down-regulates polycyclic aromatic hydrocarbon-induced cytochrome P450 1A1 in mouse liver and lung. Exp Mol Med 28, 167–172 (1996). https://doi.org/10.1038/emm.1996.26
- diallyl sulfide
- cytochrome P450