Lawrence T S, Chang E Y, Davis M A, Stetson P L, Ensminger W D
Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor 48109, USA.
Int J Radiat Oncol Biol Phys. 1996 Feb 1;34(3):617-21. doi: 10.1016/0360-3016(95)02117-5.
Although we have characterized the incorporation of the thymidine analog bromodeoxyuridine (BrdUrd) into human colon cancer xenografts under a wide variety of conditions, little is known about the effect of radiation on subsequent incorporation. Because clinical protocols include, as one component, BrdUrd administration after radiation, it was important to confirm that irradiation did not prevent subsequent BrdUrd incorporation. Therefore, we studied the effect of irradiation on BrdUrd incorporation into HT29 human colon cancer xenografts.
Two types of experiments were performed. In the first, the effect of radiation on subsequent incorporation was measured. Tumors received doses of 0, 2, 8, and 12 Gy, animals were infused with BrdUrd for 4 days, and incorporation was assessed at the end of the infusion. In the second, the effect of radiation on the elimination of BrdUrd from tumors was determined. Animals were infused with BrdUrd, tumors were irradiated with either 0 or 12 Gy, and tumor incorporation of BrdUrd was measured 1 and 3 days later.
Radiation affected neither the incorporation into nor the elimination of BrdUrd from human tumor xenografts.
These findings support the feasibility of clinical trials interdigitating BrdUrd infusion and radiation.
尽管我们已经在多种条件下对胸苷类似物溴脱氧尿苷(BrdUrd)掺入人结肠癌异种移植瘤的情况进行了表征,但对于辐射对后续掺入的影响知之甚少。由于临床方案中包括在放疗后给予BrdUrd这一环节,因此确认照射不会阻止后续BrdUrd的掺入非常重要。因此,我们研究了照射对BrdUrd掺入HT29人结肠癌异种移植瘤的影响。
进行了两种类型的实验。在第一个实验中,测量了辐射对后续掺入的影响。肿瘤接受0、2、8和12 Gy的剂量,给动物输注BrdUrd 4天,并在输注结束时评估掺入情况。在第二个实验中,确定了辐射对肿瘤中BrdUrd消除的影响。给动物输注BrdUrd,肿瘤接受0或12 Gy的照射,并在1天和3天后测量肿瘤中BrdUrd的掺入情况。
辐射对人肿瘤异种移植瘤中BrdUrd的掺入和消除均无影响。
这些发现支持了将BrdUrd输注与放疗穿插进行的临床试验的可行性。