An oil spill accident happened to a Russian tanker Nakhodka with a cargo of
heavy oil type C in the Sea of Japan on January, 1997 and the spilled oil
severely polluted the coast of Japan and damaged the environment. In this s
tudy, androgenic and antiandrogenic activities of C-heavy oil crude extract
s prepared with ethanol were evaluated on two androgen-responsive cell line
s, a Shionogi mouse mammary carcinoma SC115 and a human prostate carcinoma
LNCaP. Oils used in this study were the Nakhodka and a commercial C-heavy o
ils. Assessment of androgenic and antiandrogenic activities was made on the
basis of effect on proliferation (SC115) and prostate specific antigen (PS
A) production (LNCaP cells) in the absence and the presence of 0.5 nM dihyd
rotestosterone (DHT). While both extracts exerted almost no effect on the p
roliferation and PSA production of SC115 and LNCaP cells in the absence of
DHT, the extracts significantly inhibited the DHT-induced proliferation and
PSA production of the cells in the presence of DHT, indicating that the C-
heavy oils contains antiandrogenic compounds. It has been known that androg
en receptor (AR) expressed in LNCaP cells has mutation in ligand-binding do
main and consequently, its transcription promoting action after ligand-bind
ing is different from that of normal AR. Cyproterone acetate (CA), an andro
gen antagonist, and 17 beta-estradiol, an estrogen, stimulated PSA producti
on and their stimulatory effects were additive to that of DHT in LNCaP cell
s, while CA inhibited DHT-induced proliferation and 17 beta-estradiol showe
d quite weak agonistic effect in SC115 cells. Therefore, a part of antiandr
ogenic effects of the oil extracts was considered to be mediated through me
chanism other than direct transcriptional activation by activated AR. Then,
a few polycyclic aromatic hydrocarbons (PAHs) that are considered not to b
ind to AR were examined for their androgenic and antiandrogenic effect. Ben
zo[a]anthracene (BaA), benzo[k]fluoranthene (BkF) and benzo[a]pyrene (BaP)
suppressed DHT-induced proliferation and PSA production of SC115 and LNCaP
cells in a concentration-dependent manner. The antiandrogenic effect of the
two heavy oil extracts was considered to be due in part to PAHs. (C) 2000
Elsevier Science S.A. All rights reserved.