The binding of the 14C-labelled-ethylene and -pyrimidine moieties of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) to the biological macromolecules was studied with the AH-130 hepatoma-bearing rats, suspension of AH-130 cells, and isolated nucleic acids and proteins. In all systems examined, a significant level of the binding of the [14C]ethylene of ACNU to nucleic acids, probably due to alkylation, was observed. In contrast, the extent of the binding of the [14C]-pyrimidine was negligible. When a compound lacking the 4-amino group of ACNU (deamino-ACNU) was used for the binding study, relatively higher binding of this compound than that of ACNU to [14C]lysine was observed. It was revealed, therefore, that the low binding of ACNU to proteins could be due to instantaneous depletion of an isocyanate-intermediate, according to the formation of an intramolecularly carbamoylated product with the amino-group on the pyrimidine ring of ACNU molecule during incubation. This could be the molecular basis for the low carbamoylating activity of ACNU in vivo and in vitro, and the antitumor action of ACNU would be dependent on its alkylating activity only.

中文翻译：

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3-[（4-氨基-2-甲基-5-嘧啶基）甲基] -1-（2-氯乙基）-1-亚硝基脲盐酸盐与核酸和蛋白质的相互作用。

3-[（4-氨基-2-甲基-5-嘧啶基）甲基] -1-（2-氯乙基）-1-亚硝基脲盐酸盐（ACNU）的14C标记的乙烯和-嘧啶部分的结合用具有AH-130的肝癌的大鼠，AH-130细胞的悬浮液以及分离的核酸和蛋白质研究了生物大分子。在所有检查的系统中，可能是由于烷基化，观察到ACNU的[14C]乙烯与核酸的结合水平很高。相反，[14C]-嘧啶的结合程度可忽略不计。当使用缺乏ACNU的4-氨基基团的化合物（deamino-ACNU）进行结合研究时，发现该化合物与ACNU的[14C]赖氨酸的结合相对较高。因此，据透露，认为在培养过程中，ACNU分子的嘧啶环上带有氨基的分子内氨基甲酰化产物的形成，表明ACNU与蛋白质的低结合性可能是由于异氰酸酯中间体的瞬时消耗所致。这可能是ACNU在体内和体外低氨基甲酰化活性的分子基础，而ACNU的抗肿瘤作用将仅取决于其烷基化活性。