Effects of polychlorinated dibenzo- p-dioxin and dibenzofuran congeners in human lymphoblastoid cells on aryl hydrocarbon hydroxylase activity

Abstract

The separate and concurrent effects of polychlorinated dibenzo- p-dioxin (PCDD) and dibenzofuran (PCDF) congeners on aryl hydrocarbon hydroxylase (AHH) activity in human lymphoblastoid cells were examined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) induced AHH activity about 9-fold acetone-treated AHH activity, while octachlorodibenzo- p-dioxin (octaCDD) did not affect the AHH activity and 2,4,6,8-tetrachlorodibenzofuran (2,4,6,8-tetraCDF) reduced the AHH activity by 3470. The concurrent effect of 2,3,7,8-tetraCDD with 1,3,6,8-tetraCDD on AHH inducibility was much smaller than expected. The concurrent effect of 2,3,7,8-tetraCDD with 2,4,6,8-tetraCDF, octaCDD or 3,3′,4,4′,5,5′-hexaCB was as much as the effect of 2,3,7,8-tetraCDD alone. There was a difference between 3-methylcholanthrene (MC) and 2,3,7,8-tetraCDD in the concurrent effects of 3-methylsulfone-3′,4,4′,5-tetraCB (3-MSF-3′,4,4′,5-tetraCB) on AHH activity. The concurrent effect of MC with 3-MSF-3′,4,4′,5-tetraCB on AHH activity was equal to the effect of MC alone while that of 2,3,7,8-tetraCDD and 3-MSF-3′,4,4′,5-tetraCB on AHH activity was inhibitory. These results imply that congeners of PCDD and PCDF are considered to be more or less effective and isozymes of cytochrome P450, key enzymes for the AHH, induced by them are differently inhibited.