tretinoin and 4-dichlorobenzene

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.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Chlorobenzenes; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2B1; Dose-Response Relationship, Drug; Endocrine Disruptors; Enzyme Induction; Estradiol; Estrogen Receptor alpha; Estrogen Receptor Modulators; Female; Liver; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred ICR; Organ Size; Ovary; Peroxidase; Rats; Rats, Sprague-Dawley; Receptors, Aryl Hydrocarbon; Reproducibility of Results; Species Specificity; Tretinoin; Uterus