Ferguson L R, van Zijl P
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
Mutat Res. 1988 Apr;204(4):655-63. doi: 10.1016/0165-1218(88)90069-9.
Nitracrine is used clinically as an antitumour agent, and analogues are actively being developed in some laboratories. The mutagenic activity of 9-[(3-dimethylaminopropyl)amino]-acridine and its 1-nitro (nitracrine), 2-, 3- and 4-nitro derivatives was evaluated at the 6-thioguanine and ouabain resistance loci in cultured Chinese hamster fibroblasts (V79-171b cell line). The des-nitro, 2- and 3-nitro caused no statistically significant mutagenic activity at either locus. Each of these 3 compounds weakly increased (approximately 2-fold) the incidence of micronuclei in the same cell line when tested at cytotoxic doses. Both the 1- and 4-nitro compounds increased the incidence of 6-thioguanine resistant cells from around 1 in 10(-6) to approximately 1 in 10(-4). The former compound significantly increased the frequency of ouabain-resistant cells. Both of these compounds were potent inducers of micronuclei in V79-171b cells, indicating high clastogenic activity. It would appear prudent to regard both of these compounds as potential human carcinogens.
硝吖啶在临床上用作抗肿瘤药物，一些实验室正在积极研发其类似物。在培养的中国仓鼠成纤维细胞（V79 - 171b细胞系）的6 - 硫鸟嘌呤和哇巴因抗性位点评估了9 - [(3 - 二甲基氨基丙基)氨基] - 吖啶及其1 - 硝基（硝吖啶）、2 - 、3 - 和4 - 硝基衍生物的诱变活性。去硝基、2 - 和3 - 硝基在这两个位点均未引起统计学上显著的诱变活性。当以细胞毒性剂量测试时，这3种化合物中的每一种在同一细胞系中均使微核发生率略有增加（约2倍）。1 - 和4 - 硝基化合物均使6 - 硫鸟嘌呤抗性细胞的发生率从约1/10⁻⁶增加到约1/10⁻⁴。前一种化合物显著增加了哇巴因抗性细胞的频率。这两种化合物都是V79 - 171b细胞中微核的有效诱导剂，表明具有高断裂活性。将这两种化合物都视为潜在的人类致癌物似乎是谨慎的做法。
