TY - JOUR
T1 - Binding of polynuclear aromatic hydrocarbons to the rat 4S cytosolic binding protein
T2 - Structure-activity relationships
AU - Kamps, C.
AU - Safe, S.
N1 - Funding Information:
The financial assistanceo f the Texas Agricultural Experiment Station, the Chester J. Reed Endowment and Center for Energy and Mineral Resources is gratefully acknowledged.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1987/2
Y1 - 1987/2
N2 - The relative competitive binding affinites of benzo[a]pyrene (B[a]P), benzo[e]pyrene, benzo[g,h,i]perylene, picene, 7,12-dimethylbenz[a]anthracene, 1,2,3,4-dibenz[a]anthracene, 1,2,5,6-dibenz[a]anthracene, perylene, 4H-cyclopenta[d,e,f]-phenanthrene, benz[a]anthracene, triphenylethylene and triptycene for the rat hepatic cytosolic 4S binding protein were determined using [3H] benzo[a]pyrene as the radioligand. With the exception of triphenlethylene, triptycene and 4H-cycolopenta[d,e,f]phenanthrene, the EC50 values for the remainder of these compounds were between 1.25 × 10-7 and 2.5 × 10-8 M with 1,2,5,6-dibenz[a]anthracene being the most active ligand. A comparison of the relative cytosolic Ah (9S) receptor binding affinities and aryl hydrocarbon hydroxylase (AHH) induction potencies of these hydrocarbons with their 4S protein binding affinities demonstrated the following: (a) five compounds, namely 1,2,5,6-dibenz[a]anthracene, 1,2,3,4-dibenz[a]anthracene, picene, benzo[a]pyrene and 3-methylcholanthrene exhibited high to moderate binding affinities for the 4S and 9S cytosolic proteins (EC50 values < 10-6 M) and induced AHH in rat hepatoma cells; (b) three compounds, namely perylene, benzo[e]pyrene and benzo[g,h,i]perylene exhibited high affinities for the 4S binding protein (1.25 × 10-7, 4.4 × 10-8 and 2.9 × 10-8 M, respectively) and low affinities (EC50 values 10-5 M) for the Ah receptor protein; (c) moreover these three compounds did not induce AHH in rat hepatoma H-4-II E cells in culture. These data suggest that the 4S binding protein may not play a significant role in AHH induction although the results do not rule out a function for this protein in the transregulation of AHH and its associated cytochromes P-450.
AB - The relative competitive binding affinites of benzo[a]pyrene (B[a]P), benzo[e]pyrene, benzo[g,h,i]perylene, picene, 7,12-dimethylbenz[a]anthracene, 1,2,3,4-dibenz[a]anthracene, 1,2,5,6-dibenz[a]anthracene, perylene, 4H-cyclopenta[d,e,f]-phenanthrene, benz[a]anthracene, triphenylethylene and triptycene for the rat hepatic cytosolic 4S binding protein were determined using [3H] benzo[a]pyrene as the radioligand. With the exception of triphenlethylene, triptycene and 4H-cycolopenta[d,e,f]phenanthrene, the EC50 values for the remainder of these compounds were between 1.25 × 10-7 and 2.5 × 10-8 M with 1,2,5,6-dibenz[a]anthracene being the most active ligand. A comparison of the relative cytosolic Ah (9S) receptor binding affinities and aryl hydrocarbon hydroxylase (AHH) induction potencies of these hydrocarbons with their 4S protein binding affinities demonstrated the following: (a) five compounds, namely 1,2,5,6-dibenz[a]anthracene, 1,2,3,4-dibenz[a]anthracene, picene, benzo[a]pyrene and 3-methylcholanthrene exhibited high to moderate binding affinities for the 4S and 9S cytosolic proteins (EC50 values < 10-6 M) and induced AHH in rat hepatoma cells; (b) three compounds, namely perylene, benzo[e]pyrene and benzo[g,h,i]perylene exhibited high affinities for the 4S binding protein (1.25 × 10-7, 4.4 × 10-8 and 2.9 × 10-8 M, respectively) and low affinities (EC50 values 10-5 M) for the Ah receptor protein; (c) moreover these three compounds did not induce AHH in rat hepatoma H-4-II E cells in culture. These data suggest that the 4S binding protein may not play a significant role in AHH induction although the results do not rule out a function for this protein in the transregulation of AHH and its associated cytochromes P-450.
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U2 - 10.1016/0304-3835(87)90003-6
DO - 10.1016/0304-3835(87)90003-6
M3 - Article
C2 - 3028605
AN - SCOPUS:0023112933
SN - 0304-3835
VL - 34
SP - 129
EP - 137
JO - Cancer Letters
JF - Cancer Letters
IS - 2
ER -