Chemotherapy patients often experience chemosensory changes during and after drug therapy. The chemotherapy drug, cyclophosphamide (CYP), has known cytotoxic effects on sensory and proliferating cells of the taste system. Like the taste system, cells in the olfactory epithelia undergo continuous renewal. Therefore, we asked if a single injection of 75 mg/kg CYP would affect cell proliferation in the anterior dorsomedial region of the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) from 0-125 days after injection. Both epithelia showed a decrease in Ki67 labeled cells compared to controls at day 1 and no Ki67+ cells at day 2 post injection. In the sensory layer of the MOE, cell proliferation began to recover four days after CYP injection and by six days, the rate of proliferation was significantly greater than controls. Ki67+ cells peaked 30 days post injection, then declined to control levels at day 45. Similar temporal sequences of initial CYP-induced suppression of cell proliferation followed by elevated rates peaking 30-45 days post injection were seen in the sustentacular layer of the MOE and all three areas (sensory, sustentacular, marginal) of the VNO. CYP affected proliferation in the sensory layer of the MOE more than the sustentacular layer and all three areas of the VNO. These findings suggest that chemotherapy involving CYP is capable of affecting cell renewal of the olfactory system and likely contributes to clinical loss of function during and after chemotherapy.

中文翻译：

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环磷酰胺对嗅上皮细胞的增殖具有长期影响。


化疗患者在药物治疗期间和之后经常会经历化学感觉变化。化疗药物环磷酰胺 (CYP) 对味觉系统的感觉细胞和增殖细胞具有已知的细胞毒性作用。与味觉系统一样，嗅觉上皮细胞也在不断更新。因此，我们询问单次注射75 mg/kg CYP是否会影响注射后0-125天的主嗅上皮（MOE）和犁鼻器（VNO）前背内侧区域的细胞增殖。与对照组相比，注射后第 1 天，两种上皮细胞中 Ki67 标记细胞均有所减少，而注射后第 2 天则没有 Ki67+ 细胞。在 MOE 的感觉层中，细胞增殖在 CYP 注射后四天开始恢复，到六天时，增殖率显着高于对照组。 Ki67+ 细胞在注射后 30 天达到峰值，然后在第 45 天下降到对照水平。在 MOE 的支撑层和VNO 的所有三个区域（感觉区域、支撑区域、边缘区域）。 CYP 对 MOE 感觉层增殖的影响大于支持层和 VNO 的所有三个区域。这些发现表明，涉及 CYP 的化疗能够影响嗅觉系统的细胞更新，并可能导致化疗期间和化疗后的临床功能丧失。