Levin V A, Kabra P A, Freeman-Dove M A
Cancer Chemother Pharmacol. 1978;1(4):233-42. doi: 10.1007/BF00257156.
To obtain a clearer definition of the relationship between the structure of BCNU and CCNU and their antitumor activity, we determined the uptake, distribution, and tissue/plasma partition ratios of both compounds in normal organs and intracerebral (ic) 9L tumors in rats. Greater uptake, distribution, and tissue/plasma partition ratios were obtained for parent CCNU in fat, liver, and brain, and for parent BCNU in kidney. CCNU distributes more rapidly and extensively than BCNU only in fatty tissues. BCNU distributed more extensively in kidney and liver. Rats received bolus IV injections of 14C-labeled BCNU or CCNU in increasing doses; measurements taken 30 min after injection showed that three- to fourfold more BCNU than CCNU was bound to nucleic acids in brain and ic 9L tumor tissue. Because the chloroethyl group is the alkylating moiety for both drugs, these findings implied that BCNU biotransformed to its reactive intermediate more rapidly than did CCNU. These observations, together with previous findings, indicate that one reason for the greater effectiveness of BCNU than CCNU against ic 9L tumors is its superior ability to form an intermediate that can bind to ic 9L tumor cell nucleic acids.
为了更清楚地界定卡莫司汀（BCNU）和洛莫司汀（CCNU）的结构与其抗肿瘤活性之间的关系，我们测定了这两种化合物在大鼠正常器官和脑内（ic）9L肿瘤中的摄取、分布以及组织/血浆分配比。在脂肪、肝脏和脑中，CCNU母体的摄取、分布以及组织/血浆分配比较高；在肾脏中，BCNU母体的摄取、分布以及组织/血浆分配比较高。仅在脂肪组织中，CCNU的分布比BCNU更快、更广泛。BCNU在肾脏和肝脏中的分布更广泛。给大鼠静脉推注递增剂量的14C标记的BCNU或CCNU；注射后30分钟进行的测量表明，在脑和ic 9L肿瘤组织中，与核酸结合的BCNU比CCNU多三到四倍。由于氯乙基是这两种药物的烷基化部分，这些发现表明BCNU比CCNU更快地生物转化为其反应性中间体。这些观察结果与先前的发现一起表明，BCNU比CCNU对ic 9L肿瘤更有效的一个原因是其形成能够与ic 9L肿瘤细胞核酸结合的中间体的能力更强。
