Estrogenic activities of nitrophenols in diesel exhaust particles.
We recently isolated 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP) from diesel exhaust particles (DEP) and identified them as vasodilators. Because these compounds are alkylphenolic derivatives that might mimic hormones, we evaluated their estrogenic activity by using recombinant yeast screens, myometrial contractility assays, and in vivo uterotrophic assays. Recombinant yeast screen assays showed that both PNMC and PNMPP possess estrogenic activity. Furthermore, ovariectomized 25-day-old immature female rats injected with PNMC and PNMPP subcutaneously for 2 days showed significant increases in uterine weight among those receiving 100 mg/kg PNMC and 0.1 and 1.0 mg/kg PNMPP. To clarify further the estrogenic activity of PNMC and PNMPP, rat uterine horns were monitored in organ bath chambers for myometrial contractility in response to oxytocin (OT). Significant differences occurred in the initial and maximum contractilities to OT at 0.25 and 25 mIU/ml in uterine horns obtained from animals treated with 100 mg/kg PNMC and in the maximum contractilities to OT at 0.025, 0.25, and 25 mIU/ml in those from rats treated with 0.1 mg/kg PNMPP. These results clearly demonstrated that PNMC and PNMPP in DEP have estrogenic activity both in vitro and in vivo and might therefore be considered as endocrine-disrupting chemicals.
Furuta
Chie
C
Laboratory of Veterinary Physiology, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Suzuki
Akira K
AK
Taneda
Shinji
S
Kamata
Kazuyuki
K
Hayashi
Hideyuki
H
Mori
Yoki
Y
Li
Chunmei
C
Watanabe
Gen
G
Taya
Kazuyoshi
K
D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003408:Cresols / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D009596:Nitrophenols / Q000008:administration & dosage / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000033:anatomy & histology; D001335:Vehicle Emissions
C494060:4-nitro-3-phenylphenol; D001713:Biphenyl Compounds; D003408:Cresols; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D009596:Nitrophenols; D011994:Recombinant Proteins; D001335:Vehicle Emissions; C008636:4-nitro-3-cresol; D004958:Estradiol; D007986:Luteinizing Hormone