Antiestrogenic effect of paradichlorobenzene in immature mice and rats.
A significant increase/decrease in uterine and ovarian weights was occasionally seen in immature mice and rats subcutaneously administered paradichlorobenzene (PDCB) at doses of 22-67 mg/kg/day, but the results were not necessarily reproducible. PDCB at a dose of 800 mg/kg/day always reduced uterine and ovarian weights. Intraperitoneal PDCB at doses more than 400 mg/kg/day significantly inhibited the uterotrophic effect of beta-estradiol (E2) in CD-1 (ICR) mice. E2-induced uterotrophy was dose-dependently prevented by 204-400 mg PDCB/kg/day in C57BL/6N (Ah responsive) mice but not DBA/2N (Ah non-responsive) mice. While PDCB did not bind to estrogen receptor (ER(alpha)) up to 10(-3) M. Hepatic ethoxyresorufin-O-deethylase in adult female C57BL/6N mice was induced by i.p. administration of PDCB. Induction activity of PDCB may be 10(5)-10(6) times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. These results suggest that PDCB is a weak antiestrogenic/antiuterotrophic compound possibly due to ER modulation through arylhydrocarbon receptor.
Takahashi
Osamu
O
Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health, 24-1 Hyakunincho 3-chome, Shinjuku-ku, Tokyo, 169-0073, Japan. osamu_takahashi@member.metro.tokyo.jp
Oishi
Shinshi
S
Yoneyama
Masako
M
Ogata
Akio
A
Kamimura
Hisashi
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002722:Chlorobenzenes / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism*; D020847:Estrogen Receptor Modulators / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism; D015203:Reproducibility of Results; D013045:Species Specificity; D014212:Tretinoin / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
D051792:Basic Helix-Loop-Helix Proteins; D002722:Chlorobenzenes; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D052244:Endocrine Disruptors; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D009195:Peroxidase; D018336:Receptors, Aryl Hydrocarbon; D014212:Tretinoin; C484722:Ahr protein, mouse; C018511:4-dichlorobenzene