Cancer is often treated with broad-spectrum cytotoxic drugs that not only eradicate cancerous cells but also have detrimental side effects. One of these side effects, disruption of the olfactory system, impedes a patient’s ability to smell, perceive flavor, and ultimately may interfere with their nutritional intake and recovery from cancer. Recent studies reported that the chemotherapy drug, cyclophosphamide (CYP), can damage gustatory epithelia and disrupt cell proliferation in olfactory epithelia. In this study, we asked if CYP altered globose and horizontal basal cell proliferation in the murine main olfactory epithelium (MOE) and vomeronasal organ (VNO). We used antibodies for Ki67, a marker strictly associated with cell proliferation, and Keratin 5, a marker for the cytoskeleton of horizontal basal cells. Our results revealed a significant CYP-induced decrease in the number of proliferative cells in both epithelia, especially globose basal cells in the MOE, within the first 1–2 days postinjection. Recovery of cell renewal was apparent 6 days after injection. The immunohistochemical markers showed significantly higher levels of globose and horizontal basal cell proliferation in CYP-injected mice at 14 and 30 days postinjection compared with control mice. The prolonged proliferative activation of globose and horizontal basal cells suggests that, besides altering proliferation of olfactory epithelia, the epithelial substrate needed for successful cell renewal may be adversely affected by CYP.

中文翻译：

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环磷酰胺对嗅觉上皮细胞基础细胞增殖的瞬时作用。

癌症通常用广谱的细胞毒性药物治疗，这种药物不仅可以根除癌细胞，而且还具有有害的副作用。这些副作用之一是嗅觉系统的破坏，阻碍了患者的嗅觉，感知味道的能力，最终可能会干扰患者的营养摄入和癌症康复。最近的研究报道，化疗药物环磷酰胺（CYP）可以破坏味觉上皮并破坏嗅觉上皮中的细胞增殖。在这项研究中，我们问CYP是否改变了小鼠主要嗅上皮（MOE）和犁鼻器官（VNO）中的球蛋白和水平基底细胞增殖。我们将抗体用于Ki67（一种与细胞增殖严格相关的标志物）和角蛋白5（一种用于水平基底细胞的细胞骨架的标志物）的抗体。我们的研究结果表明，在注射后的前1到2天内，CYP诱导的两个上皮细胞（特别是MOE中的球状基底细胞）增殖细胞数量均显着减少。注射后6天，细胞更新的恢复明显。免疫组化标记显示，与对照组相比，CYP注射小鼠在注射后14和30天的球蛋白水平和水平基底细胞增殖水平显着提高。球蛋白和水平基底细胞的增殖活性延长表明，除了改变嗅觉上皮细胞的增殖外，成功更新细胞所需的上皮底物可能会受到CYP的不利影响。注射后6天，细胞更新的恢复明显。免疫组化标记显示，与对照组相比，CYP注射小鼠在注射后14和30天的球蛋白水平和水平基底细胞增殖水平显着提高。球蛋白和水平基底细胞的增殖活性延长表明，除了改变嗅觉上皮细胞的增殖外，成功更新细胞所需的上皮底物可能会受到CYP的不利影响。注射后6天，细胞更新的恢复明显。免疫组化标记显示，与对照组相比，CYP注射小鼠在注射后14和30天的球蛋白水平和水平基底细胞增殖水平显着提高。球蛋白和水平基底细胞的增殖活性延长表明，除了改变嗅觉上皮细胞的增殖外，成功更新细胞所需的上皮底物可能会受到CYP的不利影响。