Ardenne M, Reitnauer P G
Arzneimittelforschung. 1975 Sep;25(9):1369-79.
A report is given on the recent discovery of outstanding immunological properties in BA 1 [N-(2-cyanoethylene)-urea] having a (low) molecular mass M = 111.104. Experiments in 214 DS carcinosarcoma bearing Wistar rats have shown that BA 1, at a dosage of only about 12 percent LD50 (150 mg kg) and negligible lethality (1.7 percent), results in a recovery rate of 40 percent without hyperglycemia and, in one test, of 80 percent with hyperglycemia. Under otherwise unchanged conditions the reference substance ifosfamide (IF) -- a further development of cyclophosphamide -- applied without hyperglycemia in its most efficient dosage of 47 percent LD50 (150 mg kg) brought about a recovery rate of 25 percent at a lethality of 18 percent. (Contrary to BA 1, 250-min hyperglycemia caused no further improvement of the recovery rate.) However this comparison is characterized by the fact that both substances exhibit two quite different (complementary) mechanisms of action. Leucocyte counts made after application of the said cancerostatics and dosages have shown a pronounced stimulation with BA 1 and with ifosfamide, the known suppression in the post-therapeutic interval usually found with standard cancerostatics. In combination with the cited plaque test for BA 1, blood pictures then allow conclusions on the immunity status. Since IF can be taken as one of the most efficient cancerostatics--there is no other chemotherapeutic known up to now that has a more significant effect on the DS carcinosarcoma in rats -- these findings are of special importance. Finally, the total amount of leucocytes and lymphocytes as well as their time behaviour was determined from the blood picture of tumour-free rats after i.v. application of BA 1. The thus obtained numerical values clearly show that further research work on the prophylactic use of this substance seems to be necessary and very promising.
本文报道了最近发现的低分子量（M = 111.104）的BA 1 [N-(2-氰基乙烯基)-脲]具有卓越的免疫特性。在214只患有DS癌肉瘤的Wistar大鼠身上进行的实验表明，BA 1仅以约12%的半数致死剂量（LD50，150毫克/千克）给药，致死率可忽略不计（1.7%），能使40%的大鼠康复且无高血糖现象，在一项实验中，出现高血糖时康复率为80%。在其他条件不变的情况下，参比物质异环磷酰胺（IF）——环磷酰胺的进一步衍生物，在无高血糖状态下以其最有效剂量47% LD50（150毫克/千克）给药，致死率为18%时康复率为25%。（与BA 1不同，250分钟的高血糖并未使康复率进一步提高。）然而，这种比较的特点是，两种物质表现出两种截然不同（互补）的作用机制。在使用上述抗癌药物及相应剂量后进行的白细胞计数显示，BA 1和异环磷酰胺均有明显的刺激作用，这与标准抗癌药物通常在治疗后间隔期出现的抑制作用不同。结合所引用的针对BA 1的空斑试验，血液图片有助于推断免疫状态。由于IF可被视为最有效的抗癌药物之一——目前已知没有其他化疗药物对大鼠DS癌肉瘤有更显著的效果——这些发现具有特殊重要性。最后，通过对静脉注射BA 1后的无瘤大鼠血液图片进行分析，确定了白细胞和淋巴细胞的总数及其随时间的变化情况。由此获得的数值清楚地表明，对该物质预防性用途的进一步研究工作似乎很有必要且前景广阔。
