Oxidized sterols inhibit the formation of podophyllin-induced metaphase figures in mouse vaginal epithelia.
The antimitotic activity of oxidized derivatives of cholesterol was investigated using an assay developed by Van Scott and Bonder. In this assay, a drug that has antimitotic activity and is not a metaphase-blocking agent will inhibit the formation of podophyllin-induced metaphase figures, as counted on histologic specimens. Mouse vaginal epithelia were classified as being estrogen or progesterone predominant on the basis of histologic criteria. Podophyllin-injected mice in the estrogenic phase of the estrus cycle demonstrated high metaphase-figure counts, with an average of 284.86 +/- 132.01. In this group, all intravaginally administered compounds, inhibited the formation of metaphase figures, including a propylene-glycol ethanol vehicle (60% suppression); thus, it is concluded that animals in this phase are not a suitable model for assaying antimitotic activity. Mice in the progesterone-predominant phase of the estrus cycle had lower counts of podophyllin-induced metaphase figures, i.e., 142.13 +/- 39.29. In this group, 25-OH-cholesterol was the most effective inhibitor (59% suppression), followed by 7-ketocholesterol (48% suppression) and methotrexate (40% suppression). Cholesterol (5% suppression) and vehicle (20% suppression) did not have any significant effects. Progesterone-predominant epithelium was only susceptible to methotrexate and oxidized sterols. This suggests that oxidized sterols may have antimitotic activity.
D000818:Animals; D004848:Epithelium / Q000187:drug effects; D004967:Estrogens / Q000502:physiology; D004971:Estrus; D005260:Female; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D011033:Podophyllin / Q000494:pharmacology; D011374:Progesterone / Q000502:physiology; D012007:Rectum / Q000187:drug effects; D013261:Sterols / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects*
D004967:Estrogens; D013261:Sterols; D011374:Progesterone; D011033:Podophyllin