Beal D D, Skibba J L, Whitnable K K, Bryan G T
Cancer Res. 1976 Aug;36(8):2827-31.
Studies were undertaken to determine the effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and its metabolites on the growth and macromolecular synthesis of Novikoff hepatoma cells in culture. DTIC (3.0 mM) in light decreased the viable cell count by 90% within 96 hr. DTIC protected from light, 2-azahypoxanthine, dimethylamine, and 5-aminoimidazole-4-carboxamide, all at 3.0 mM, reduced the rate of cellular proliferation. 5-Diazoimidazole-4-carboxamide (1.0 mM) and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (3.0 mM) decreased the viable cell count by 99%. Effects on macromolecular synthesis were determined by the rate of incorporation of the appropriate 3H-labeled precursor. Results after 6 hr are given as percentage of controls. DTIC (1.0 mM) in light inhibited DNA (8%), RNA (41%), and protein (63%) synthesis. DTIC (1.0 mM) protected from light inhibited DNA (12%) and RNA (57%) synthesis. 5-Diazoimidazole-4-carboxamide (0.1 mM) inhibited DNA (1%), RNA (9%), and protein (1%) synthesis. 5-(3-Methyl-1-triazeno)imidazole-4-carboxamide (1.0 mM) inhibited DNA (72%) and protein (65%) synthesis but stimulated RNA (127%) synthesis. 2-Azahypoxanthine (1.0 mM) inhibited DNA (43%), RNA 82%) and protein (28%) synthesis. 5-Aminoimidazole-4-carboxamide (3.0 mM) stimulated DNA (354%) and RNA (266%) synthesis. These data show that DTIC is able to generate several toxic metabolites that may be responsible for its biological effects.
开展了多项研究以确定5 -（3,3 - 二甲基 - 1 - 三氮烯基）咪唑 - 4 - 甲酰胺（DTIC）及其代谢产物对培养的诺维科夫肝癌细胞生长和大分子合成的影响。光照条件下的DTIC（3.0 mM）在96小时内使活细胞数量减少了90%。避光条件下的DTIC、2 - 氮杂次黄嘌呤、二甲胺和5 - 氨基咪唑 - 4 - 甲酰胺，浓度均为3.0 mM，降低了细胞增殖速率。5 - 重氮咪唑 - 4 - 甲酰胺（1.0 mM）和5 -（3 - 甲基 - 1 - 三氮烯基）咪唑 - 4 - 甲酰胺（3.0 mM）使活细胞数量减少了99%。通过合适的3H标记前体的掺入速率来确定对大分子合成的影响。6小时后的结果以对照的百分比给出。光照条件下的DTIC（1.0 mM）抑制DNA（8%）、RNA（41%）和蛋白质（63%）合成。避光条件下的DTIC（1.0 mM）抑制DNA（12%）和RNA（57%）合成。5 - 重氮咪唑 - 4 - 甲酰胺（0.1 mM）抑制DNA（1%）、RNA（9%）和蛋白质（1%）合成。5 -（3 - 甲基 - 1 - 三氮烯基）咪唑 - 4 - 甲酰胺（1.0 mM）抑制DNA（72%）和蛋白质（65%）合成，但刺激RNA（127%）合成。2 - 氮杂次黄嘌呤（1.0 mM）抑制DNA（43%）、RNA（82%）和蛋白质（28%）合成。5 - 氨基咪唑 - 4 - 甲酰胺（3.0 mM）刺激DNA（354%）和RNA（266%）合成。这些数据表明DTIC能够产生几种可能对其生物学效应负责的有毒代谢产物。
