title: Methyl tertiary butyl ether-induced endocrine alterations in mice are not mediated through the estrogen receptor.
abstract: Chronic exposure to methyl tertiary butyl ether (MTBE) altered the rodent tumor incidence of endocrine-sensitive tissues and decreased the incidence of estrogen-dependent uterine cystic hyperplasia in mice. To test the hypothesis that changes in the incidence of tumors in female B6C3F1 mice after MTBE exposure are secondary to endocrine alterations, we exposed female mice to the carcinogenic dose of MTBE vapor (8000 ppm) for 3 or 21 days or 4 or 8 months under conditions similar to a previous 2-year bioassay. MTBE exposure significantly decreased body weight gain and ovary and pituitary weight at 4 and 8 months and uterine weight at all time points. After 8 months of exposure, MTBE significantly increased the length of the estrous cycle by increasing the mean number of days in both the estrus and the nonestrus stages. Histological evaluation of H&E-stained tissues showed a decrease in the number of uterine glands after subchronic MTBE exposure. DNA synthesis, as measured by the incorporation of 5-bromo-2'-deoxyuridine (BrdU), was decreased in uterine glandular and luminal epithelial cells after MTBE exposure for 3 or 21 days or 4 or 8 months. MTBE exposure decreased the number of epithelial layers in the cervix and vagina at all time points. DNA synthesis was decreased in cervical and vaginal epithelium after 21 days of MTBE. Decreased zona reticularis of adrenal glands was found after 4 and 8 months of MTBE exposure without changes in BrdU incorporation. MTBE did not competitively bind to estrogen receptor. MTBE exposure did not alter serum estrogen levels or alter the location or intensity of estrogen receptor immunoreactivity in the uterus, cervix, and vagina. These data indicate that while MTBE exposure causes multiple endocrine-related tissue and cellular responses, these effects are not mediated through the estrogen receptor.
authors.affiliation: Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709-2137, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Moser
authors.forename: D C
authors.initials: DC
authors.lastname: Wolf
authors.forename: M
authors.initials: M
authors.lastname: Sar
authors.forename: K W
authors.initials: KW
authors.lastname: Gaido
authors.forename: D
authors.initials: D
authors.lastname: Janszen
authors.forename: T L
authors.initials: TL
authors.lastname: Goldsworthy
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002584:Cervix Uteri / Q000187:drug effects / Q000473:pathology; D004261:DNA Replication / Q000187:drug effects; D004702:Endocrine Glands / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000187:drug effects; D005260:Female; D008738:Methyl Ethers / Q000633:toxicity*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism*; D014621:Vagina / Q000187:drug effects / Q000473:pathology
chemical_list: D002273:Carcinogens; D008738:Methyl Ethers; D011960:Receptors, Estrogen; C043243:methyl tert-butyl ether; D004958:Estradiol