Strain differences in vaginal responses to the xenoestrogen bisphenol A.
Bisphenol A (BPA) is the monomer component of polycarbonate plastics and epoxy resins; human exposure derives from leachate in foodstuffs packaged in certain plastics or from epoxy-based dental appliances. BPA stimulates prolactin secretion in Fischer 344 (F344) rats but not in Sprague-Dawley (S-D) rats. The present studies were performed to determine if another classic estrogen target tissue, the rat vagina, responds to BPA in a strain-specific manner. In F344 rats BPA increased DNA synthesis in vaginal epithelium with a median effective dose (ED(50)) of 37.5 mg/kg body weight; DNA synthesis was not stimulated in S-D rats by any dose tested. Clearance of (3)H-BPA from blood followed the same time course in both strains of rats, with a half-life of 90 min. Scatchard analysis of [(3)H]estradiol binding showed no strain differences in concentration or affinity of the vaginal estrogen receptor. BPA increased the level of mRNA for the immediate early gene, c-fos, with similar dose-response curves in both rat strains. Thus, F344 and S-D rats exhibit differences in sensitivity to BPA at the level of cell proliferation in the vaginal epithelium. However, metabolic clearance of BPA and the early events that lead to the proliferative response, receptor-ligand interaction and induction of immediate early genes, show no strain differences. These observations suggest that differences in intermediate effects must account for the difference in sensitivity of the proliferative response to the xenoestrogen. Furthermore, these results point to the need for caution in choosing a suitable end point and animal model when seeking to test the estrogenic effects of xenobiotics.
Long
X
X
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5196, USA.
Steinmetz
R
R
Ben-Jonathan
N
N
Caperell-Grant
A
A
Young
P C
PC
Nephew
K P
KP
Bigsby
R M
RM
D000818:Animals; D001559:Benzhydryl Compounds; D002455:Cell Division / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D005260:Female; D016762:Genes, fos / Q000235:genetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D010636:Phenols / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014621:Vagina / Q000166:cytology* / Q000187:drug effects*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D012333:RNA, Messenger; C006780:bisphenol A; D000098826:Bisphenol A Compounds