Jd. Mckinney et Cl. Waller, POLYCHLORINATED-BIPHENYLS AS HORMONALLY ACTIVE STRUCTURAL ANALOGS, Environmental health perspectives, 102(3), 1994, pp. 290-297
Among the environmental chemicals that may be able to disrupt the endo
crine systems of animals and humans, the polychlorinated biphenyls (PC
Bs) are a chemical class of considerable concern. One possible mechani
sm by which PCBs may interfere with endocrine function is their abilit
y to mimic natural hormones. These actions reflect a close relationshi
p between the physicochemical properties encoded in the PCB molecular
structure and the responses they evoke in biological systems. These ph
ysicochemical properties determine the molecular reactivities of PCBs
and are responsible for their recognition at biological acceptors and
receptors, as well as for triggering molecular mechanisms that leat to
tissue response. ''Coplanarity'' of PCB phenyl rings and ''laterality
'' of chlorine atoms are important structural features determining spe
cific binding behavior with proteins and certain toxic responses in bi
ological systems. We compare qualitative structure-activity relationsh
ips for PCBs with the limited information on the related non-coplanar
chlorinated diphenyl ethers, providing further insights into the natur
e of the molecular recognition processes and support for the structura
l relationship of PCBs to thyroid hormones. Steroidlike activity requi
res conformational restriction and possibly hydroxylation. We offer so
me simple molecular recognition models to account for the importance o
f these different structural features in the structure-activity relati
onships that permit one to express PCB reactivities in terms of dioxin
, thyroxine, and estradiol equivalents. The available data support the
involvement of PCBs as mimics of thyroid and other steroidal hormones
. The potential for reproductive and developmental toxicity associated
with human exposure to PCBs is of particular concern.