Ludwig R, Frei E, Kimmig B, Brandeis W E
University Childrens Hospital, Heidelberg, Federal Republic of Germany.
Blut. 1987 Dec;55(6):483-8. doi: 10.1007/BF00320216.
The mechanism responsible for the toxic late effects of cranial irradiation, followed by the administration of systemic methotrexate (MTX) on brain tissue, is still under discussion. We studied the influence of X-irradiation on dihydrofolate reductase (E.C. 1.5.1.3) activity (DHFR), the enzyme inhibited by MTX. New Zealand white rabbits, 6-9 weeks old, underwent 24 Gy fractionated or 20 Gy single-dose brain irradiation using a 60Co source. Before, immediately following, and 1, 2, 4, 12 weeks after irradiation, DHFR was measured in brain and liver tissue by a photometric assay. DHFR in brain tissue was 11.9 +/- 2.9 mU/g wet weight (ww) X h and in liver tissue 121.8 +/- 24.2 mU/g ww X h. Fractionated brain irradiation with 2 Gy per day produced no significant changes in brain DHFR. Single-dose cranial irradiation significantly decreased brain DFHR (7.3 +/- 0.6 mU/g ww X h). Suppression of the developmental increase of DHFR by X-irradiation in young rabbits could be excluded by determining the unchanged brain-to-liver ratios of DHFR in the animals with fractionated brain irradiation.
在全身应用甲氨蝶呤（MTX）之后进行颅脑照射对脑组织产生毒性远期效应的机制仍在探讨之中。我们研究了X射线照射对二氢叶酸还原酶（E.C. 1.5.1.3）（DHFR）活性的影响，MTX可抑制该酶。选用6至9周龄的新西兰白兔，使用60Co源进行24 Gy分次或20 Gy单次颅脑照射。在照射前、照射后即刻以及照射后1、2、4、12周，通过光度法测定脑和肝组织中的DHFR。脑组织中的DHFR为11.9±2.9 mU/g湿重（ww）×小时，肝组织中的为121.8±24.2 mU/g湿重（ww）×小时。每天2 Gy的分次颅脑照射未使脑DHFR发生显著变化。单次颅脑照射显著降低了脑DFHR（7.3±0.6 mU/g湿重（ww）×小时）。通过测定分次颅脑照射动物中DHFR不变的脑肝比值，可以排除X射线照射对幼兔DHFR发育性升高的抑制作用。
