Premium
Sulfur analogues of polychlorinated dibenzo‐ P ‐dioxins, dibenzofurans and diphenyl ethers as inducers of CYP1A1 in mouse hepatoma cell culture and structure‐activity relationships
Author(s) -
Kopponen Paivi,
Sinkkonen Seija,
Poso Antti,
Gynther Jukka,
Karenlampi Sirpa
Publication year - 1994
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.5620130917
Subject(s) - chemistry , sulfur , inducer , potency , aryl , microsome , ec50 , enzyme inducer , stereochemistry , biochemistry , enzyme , in vitro , organic chemistry , gene , alkyl
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