Paradoxical down-regulation of benzoapyrene-mediated DNA-adduct formation by 2,3,7,8-tetrachlorodibenzo-p-dioxin in human lung cells

摘要

Pretreatment of H358 cells with 10 nM TCDD resulted in a decrease in B[a]PDE-dGuo adduct formation with either 2 (mu)M (-)-B[a]P-7,8-dihydrodiol or (+-)-B[a]PDE treatment. Therefore, the decrease in DNA-adduct formation is not a result of the CYP1A1/1B1 metabolism pathway. A reversed-phase LC-MS/MS method was developed to detect the formation of B[a]P-GSH adduct isomers in H358 and HepG2 cell lines. There is an inverse relationship between B[a]PDE-dGuo formation and B[a]P-GSH formation in H358 cells. TCDD induction results in and increase in H358 B[a]P-GSH adducts, where as TCDD causes an in crease in HepG2 (+)-anti-trans-B[a]PDE-dGuo levels increase.