Sulfur analogues of polychlorinated dibenzo-p-dioxins, dibenzofurans and diphenyl ethers as inducers of CYP1A1 in mouse hepatoma cell culture and structure-activity relationships

Article abstract of DOI:10.1002/etc.5620130917

Three sulfur-containing compounds, 2,3,7,8-tetrachlorothianthrene (TCTA), 2,3,7,8-tetrachlorodibenzothiophene (TCDT), and 3,3',4,4'- tetrachlorodiphenyl sulfide (TCDPS), were analyzed for their CYP1A1-inducing potencies - measured as aryl hydrocarbon hydroxylase (AHH) and 7- ethoxyresorufin O-deethylase (EROD) activities - in mouse hepatoma cell culture Hepa-1. Marked differences in the induction potencies were observed among the three compounds studied and between 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) and its sulfur analogue. The estimated EC50 values for TCDD, TCTA, and TCDT were about 8 pM, 700 pM, and 7.5 nM, respectively. TCDPS did not elicit any AHH/EROD induction. Comparative molecular field analysis (CoMFA) was not able to predict correctly the biological potency of TCTA and TCDT. The most important reason for the poor performance of the model may be the positive point charge of sulfur in TCTA and TCDT.