Cell response endpoints enhance sensitivity of the immature mouse uterotropic assay.
Outbred immature CD-1 mice were subcutaneously (s.c.) injected once on postnatal day 17 or on postnatal days 17, 18, and 19 with 17beta-estradiol, diethylstilbestrol, tamoxifen, 4-hydroxytamoxifen, methoxychlor, the methoxychlor metabolite HPTE, nonylphenol, o,p'-DDT, endosulfan, or kepone over a wide dose range (0.1 to 1,000,000 microg/kg). On the day following the last injection, uterine weight/body weight ratios were determined and uterine tissues processed for histologic examination. All compounds except endosulfan and kepone increased uterine wet weight compared to vehicle controls; however, the dose response curve and magnitude of response varied depending on the compound. Choosing the maximum wet weight dose for each compound, uterine tissue was evaluated for epithelial cell height, epithelial and stromal cell proliferation, endometrial gland number, and induction of estrogen-inducible proteins lactoferrin and complement C3. All compounds elicited estrogen-responsive changes in these endpoints that were individually more sensitive than uterine weight alone. We conclude that these endpoints enhance the sensitivity of the uterotropic bioassay.
Newbold
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Laboratory of Toxicology, Environmental Toxicology Program, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA. newbold1@niehs.nih.gov
Jefferson
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WN
Padilla-Banks
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E
Walker
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VR
Pena
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DS
D000818:Animals; D021461:Animals, Outbred Strains; D001681:Biological Assay; D002455:Cell Division / Q000187:drug effects; D003176:Complement C3 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D004967:Estrogens / Q000008:administration & dosage / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D007279:Injections, Subcutaneous; D007781:Lactoferrin / Q000096:biosynthesis; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D018675:Toxicity Tests; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology
D003176:Complement C3; D004785:Environmental Pollutants; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D018809:Proliferating Cell Nuclear Antigen; D007781:Lactoferrin