Dunki Jacobs P B, Ruevekamp M, Varossiau F J, Hart G A, de Graaf P W
Division of Experimental Therapy, The Netherlands Cancer Institute (Antoni von Leeuwenhoek Huis), Amsterdam.
Eur J Cancer Clin Oncol. 1989 Mar;25(3):415-22. doi: 10.1016/0277-5379(89)90253-8.
The alterations in serum levels, anti-tumor activity and host toxicity of methotrexate (MTX) were tested in tumor bearing rats following a period of dietary manipulation. A protein deprived (PD) diet or a diet containing a normal protein content (NP) was administered for 5 days and MTX injected intra-peritoneally (i.p.) at the end of the 5 day period. The MTX serum levels were significantly elevated in rats which received the PD diet, as compared to NP dietary rats. This elevation correlated with an enhanced tumor response to MTX administration. In addition, bone marrow toxicity and intestinal tract toxicity, measured with flow cytometry (FCM) of the bone marrow and morphometry of the jejunal mucosa respectively was increased in rats receiving the PD diet. These results indicate that the serum clearance of MTX is delayed in animals suffering from malnutrition, leading to both enhanced tumor response and increased host toxicity.
在对荷瘤大鼠进行一段时间的饮食控制后，检测了甲氨蝶呤（MTX）的血清水平、抗肿瘤活性和宿主毒性的变化。给予蛋白质缺乏（PD）饮食或含正常蛋白质含量（NP）的饮食5天，并在5天期末腹腔注射（i.p.）MTX。与NP饮食组大鼠相比，接受PD饮食的大鼠MTX血清水平显著升高。这种升高与肿瘤对MTX给药的反应增强相关。此外，分别通过骨髓流式细胞术（FCM）和空肠黏膜形态计量学测量的骨髓毒性和肠道毒性在接受PD饮食的大鼠中增加。这些结果表明，营养不良动物中MTX的血清清除延迟，导致肿瘤反应增强和宿主毒性增加。
