Light microscopy and morphometry of vinblastine in vivo cytotoxicity in the different developmental stages of rat incisor ameloblast epithelium.
To see whether the in vivo cytotoxicity of the antimicrotubule agent vinblastine (VB) was related to the degree of differentiation in a normal secretory cell population VB cytotoxicity in the various developmental stages of rat incisor ameloblast was studied. Normal values for cell and nucleus volumes, secretory velocity, VB dose-response curves for cell death, and proliferative and secretory activity were estimated quantitatively using simple stereological methods, 18 and 72 hours after VB administration i.v. Dose-response plots for cell death in jejunal crypt cells and the reduction of secretory activity in acinar pancreatic cells were compared with those of proliferating and secretory ameloblasts. Video light microscopy was used on 2 microns Epon sections with controlled orientation and position, permitting calculation of values on a per-cell-basis or per 10(4) microns 2 epithelial basal area. Normal cell and nuclear mean volumes (range: min.-max. value) for late-differentiating ameloblasts were 557 microns 3 (528-601) and 127 microns 3 (122-136), and for secretory ameloblasts 866 microns 3 (830-886) and 144 microns 3 (142-146). Mean volume of enamel matrix secreted per cell was around 169 microns 3 (122-202) per 24 hrs. Number of cells in the late-differentiating zone was 970(928-1003) and in the secretory zone 828 (820-835) per 10(4) microns 2 epithelial basal area. Cell death after VB in the ameloblast stem cells and pancreatic acinar cells was negligible. 72 hrs after VB, the supply of dividing cells to the proliferation zone was at lower doses increased, while at 3 mg/kg it was reduced to 72% of the normal. All proliferating cells appeared to be killed at 2 mg/kg, together with 38% of the differentiating and 34% of the secretory ameloblasts, and at 3 mg/kg, 70% and 66% respectively of the non-dividing ameloblasts were killed. The secretory output (volume of enamel matrix) of the ameloblasts exposed in the differentiating stage and now transformed into secretory cells was 72 hrs after VB 2 mg/kg reduced to 45%, while that of the mature secretory ameloblasts was reduced to 42%. After VB 3 mg/kg, the differentiated ameloblast zone retained 21% of the normal secretory output, whereas there was no output from the mature cells. Maximal accumulation of zymogen granules in pancreatic acinar cells occurred at 1 mg/kg VB. Unlike to secretory ameloblasts, the morphology of pancreatic acinar cells was normalized at 72 hrs after VB.(ABSTRACT TRUNCATED AT 400 WORDS)
Winther Nielsen
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Institute of Anatomy C, University of Copenhagen, Denmark.
D000565:Ameloblasts / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D007180:Incisor / Q000254:growth & development*; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D014747:Vinblastine / Q000633:toxicity*
D014747:Vinblastine