Schmid F A, Otter G M, Mehta B M
Cancer Res. 1985 Jan;45(1):40-4.
The mutagenic and chemotherapeutic activities of the following monofunctional alkylating agents were compared in vivo: beta-chloroethylamine, dimethyl- and diethylaminoethyl chloride; methyl- and ethylmethanesulfonate; methyl- and ethylnitrosourea; and procarbazine. The bifunctional alkylating agent diethylamine 2,2'-dichloro-N-methyl-hydrochloride was used as reference. The alkylating activity was assessed by reacting with 4-(p-nitrobenzyl)pyridine, and antitumor activity was determined against L1210 in vitro and in vivo. The L1210 response, which is consistent with useful alkylating reactivity, was very marked with the two nitrosoureas and procarbazine. The nitrosoureas and, to some extent, procarbazine decreased the tumorigenicity of L1210 leukemia as evidenced by the increase in survival times with increasing numbers of treatment generations. After treatment for about five transfers (10(6) cells i.p.) with methylnitrosourea (40 mg/kg i.p. on Days 1, 3, and 5), the untreated control mice consistently survived free of tumor, whereas the treated mice died before Day 30. After treatment with ethylnitrosourea (80 mg/kg), the survival times also increased but more in the treated than in the corresponding control groups. Methylnitrosourea was most efficient in increasing the survival times and abolishing tumor transplantability. Antigenic change and loss of growth potential presumably were the reason for this increase in survival time, as indicated by tests in X-irradiated and nude mice. The fact that nitrosoureas and triazenes, besides reducing tumorigenicity, have similarities in their chemistry in that they decompose or are metabolically converted into diazohydroxides and then to carbonium ions is possibly of significance.
β-氯乙胺、二甲基和二乙氨基乙基氯；甲磺酸甲酯和乙酯；甲基和乙基亚硝基脲；以及丙卡巴肼。双功能烷化剂2,2'-二氯-N-甲基-盐酸二乙胺用作对照。通过与4-(对硝基苄基)吡啶反应评估烷化活性，并在体外和体内测定对L1210的抗肿瘤活性。L1210反应与有用的烷化反应性一致，在两种亚硝基脲和丙卡巴肼中非常明显。亚硝基脲以及在一定程度上丙卡巴肼降低了L1210白血病的致瘤性，这通过随着治疗代数增加存活时间的延长得到证明。在用甲基亚硝基脲（第1、3和5天腹腔注射40mg/kg）处理约五次传代（腹腔注射10(6)个细胞）后，未处理的对照小鼠一直存活且无肿瘤，而处理过的小鼠在第30天前死亡。用乙基亚硝基脲（80mg/kg）处理后，存活时间也增加了，但处理组比相应对照组增加得更多。甲基亚硝基脲在延长存活时间和消除肿瘤移植性方面最有效。抗原变化和生长潜能丧失可能是存活时间增加的原因，X射线照射小鼠和裸鼠的试验表明了这一点。亚硝基脲和三氮烯除了降低致瘤性外，在化学性质上有相似之处，即它们分解或代谢转化为重氮氢氧化物，然后转化为碳正离子，这一事实可能具有重要意义。
