Figure 1. APC-deficient intestinal cells are resistant to low level Taxol treatment.
Mice injected with either vehicle (NT), 10, 20 or 30mg/kg Taxol IP (n≥3) were sacrificed 6h post-injection and the levels of mitotic arrest and apoptosis in intestinal crypts were scored using H+E staining. Mitotic and apoptotic index was expressed as percentage of cells per crypt. As intestinal enterocytes enter G2 phase they move out of the crypt lining and into the lumen where they will undergo mitosis and cytokinesis before retuning back to the single cell layer crypt lining. However enterocytes can undergo apoptosis anywhere in the crypt.
(a) Representative H+E staining of crypts from WT mice treated with Taxol 10mg/kg and sacrificed at 3h, 6h, 9h or 24h post-injection. Black arrows – mitotic figure, red arrow – apoptotic figure. Scale bar 20μm. (b) Mitotic index in WT intestinal crypts from mice treated with vehicle versus increasing concentrations of Taxol, p<0.026. (c) and (d) Mitotic and apoptotic index in intestinal crypts from vehicle or Taxol 10mg/kg treated WT or Cre+ APC fl/fl mice. The induction in mitotic arrest and apoptosis is significant only in WT vehicle versus treated, p<0.026. NT – vehicle-treated. (e) Representative H+E staining of crypts from Cre+ APC fl/fl mice treated with Taxol 10mg/kg and sacrificed at 3h, 6h, 9h or 24h post-injection. Scale bar 20μm.
