Urinary retention and cystitis associated with subcutaneous estradiol pellets in female nude mice.
Unexpected deaths occurred in studies involving a nude mouse model of mammary cancer that required subcutaneous implantation of 0.5 mg twenty-one-day release estrogen pellets for growth of the estrogen-dependent mammary tumor xenograft BT474c. Early deaths occurred in female nude mice and were associated with urinary retention, frequently with cystitis. Drug treatment had no effect on the incidence or severity of cystitis. Histological findings did not alter significantly over various time points following pellet implantation. Changes were not seen in males or in females receiving lower doses of estradiol even when the duration of administration was prolonged, suggesting that a threshold level was required for the onset of urinary retention. Because of the influence of estrogen on micturition, immunohistochemistry for estrogen receptor alpha (ERalpha) in the urinary bladder was carried out, which did not demonstrate any differences between females implanted with 0.5 mg twenty-one-day release estrogen pellets and nonimplanted females. Although previous publications have concentrated on possible mechanisms of action, this paper describes the histopathological changes seen in the urinary bladder of female nude mice resulting from exposure to high levels of estradiol.
Pearse
Gail
G
GSK Research and Development, The Frythe, Welwyn, Hertfordshire, UK. pearse848@btinternet.com
Frith
Jeremy
J
Randall
Kevin John
KJ
Klinowska
Teresa
T
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D003556:Cystitis / Q000150:complications*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use*; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D013997:Time Factors; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D016055:Urinary Retention / Q000150:complications*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D003692:Delayed-Action Preparations; D004343:Drug Implants; D047628:Estrogen Receptor alpha; D004958:Estradiol