Sandovsky-Losica H, Segal E
Department of Human Microbiology, University of Tel-Aviv, Israel.
J Med Vet Mycol. 1990;28(4):279-87.
The aim of the present study was to investigate whether the cytotoxic anti-cancer drugs methotrexate (MTX) or 5-fluorouracil (5FU), which affect the gastrointestinal (GI) mucosa, would also affect the ability of the damaged mucosa to bind the GI commensal yeast Candida albicans. ICR conventional female mice were treated with intraperitoneal (IP) MTX (3 mg per mouse, or intravenous (IV) 5FU (200 mg kg-1 body weight). On various days post-treatment, the small intestine was removed, tissue disks prepared and exposed for 2 h to radiolabeled C. albicans. The percent adherence of the fungus to the mucosa was assayed by determining the counts per minute (c.p.m.). An increase in the in vitro adherence of C. albicans to murine GI mucosa was found posttreatment with MTX or 5FU. The maximal increase (net increase of 40-50%) was observed on days 3-4 post-treatment with MTX or 5FU, concurrently with the maximal decrease in the total number of white blood cells (WBC) and loss in spleen weight of the treated animals (indicators of cytotoxicity of these drugs). In addition, experiments to block Candida adherence with chitin soluble extract (CSE), an inhibitor used in previous studies, were also carried out. CSE inhibited the adherence of C. albicans to the damaged GI mucosa, as well as to the GI mucosa from normal untreated mice, by up to 64% approximately. Based on these results and on findings from our previous study investigating the adherence of C. albicans to GI mucosa from irradiated mice, it can be concluded that increased adherence of C. albicans to the GI mucosa may occur in patients post-anti-cancer therapy (irradiation, or chemotherapy). This observation may partially explain the high tendency of these debilitated patients to develop systemic candidosis. Further experiments to study adherence of C. albicans to gut mucosa in vivo and eventually to inhibit this adherence with CSE are currently in progress in our laboratory.
本研究的目的是调查影响胃肠道（GI）黏膜的细胞毒性抗癌药物甲氨蝶呤（MTX）或5-氟尿嘧啶（5FU）是否也会影响受损黏膜结合胃肠道共生酵母白色念珠菌的能力。将ICR品系的雌性常规小鼠腹腔注射（IP）MTX（每只小鼠3 mg）或静脉注射（IV）5FU（200 mg/kg体重）进行处理。在处理后的不同天数，取出小肠，制备组织切片，并将其与放射性标记的白色念珠菌接触2小时。通过测定每分钟计数（c.p.m.）来检测真菌对黏膜的黏附百分比。发现用MTX或5FU处理后，白色念珠菌对小鼠胃肠道黏膜的体外黏附增加。在用MTX或5FU处理后的第3 - 4天观察到最大增加（净增加40 - 50%），同时处理动物的白细胞总数（WBC）最大减少以及脾脏重量减轻（这些药物细胞毒性的指标）。此外，还进行了用几丁质可溶性提取物（CSE）阻断念珠菌黏附的实验，CSE是先前研究中使用的一种抑制剂。CSE可使白色念珠菌对受损胃肠道黏膜以及未处理的正常小鼠胃肠道黏膜的黏附减少约64%。基于这些结果以及我们先前关于白色念珠菌对受辐照小鼠胃肠道黏膜黏附的研究结果，可以得出结论，抗癌治疗（放疗或化疗）后的患者可能会出现白色念珠菌对胃肠道黏膜黏附增加的情况。这一观察结果可能部分解释了这些虚弱患者发生系统性念珠菌病的高倾向性。我们实验室目前正在进行进一步的实验，以研究白色念珠菌在体内对肠道黏膜的黏附情况，并最终用CSE抑制这种黏附。
