Singh B, Gupta R S
Cancer Res. 1983 Feb;43(2):577-84.
The mutagenic responses of 13 antineoplastic drugs, namely, chlorambucil, busulfan, lomustine, dacarbazine, Adriamycin, daunomycin, bleomycin, VM-26, VP16-213, ellipticine, actinomycin D, mitomycin C, and cis-diamminedichloroplatinum(II) have been determined in two different assay systems in Chinese hamster ovary cells which measure mutation induction at multiple genetic loci and the frequencies of sister chromatid exchanges. The five genetic loci whose responses have been measured include those conferring resistance to 6-thioguanine (Thgr or TGr), ouabain, emetine, methylglyoxal bis(guanylhydrazone), and 5,6-dichlororibofuranosylbenzimidazole; of these, only the Thgr marker affects a function (hypoxanthine-guanine phosphoribosyltransferase, hgprt locus) which is not essential for cellular growth. All of these drugs showed a dose-dependent increase in mutation frequency at the hgprt locus, but their responses at other genetic loci differed greatly and showed marked specificity for different chemical classes of the drugs. The observed locus-specific differences in response to these drugs suggest that they may differ in terms of their accessibility or affinity to different chromosomal regions. All of these drugs also led to a significant increase in the frequency of sister chromatid exchanges, and a very good correlation was observed between the activity of these drugs in the sister chromatid exchange assay and the mutagenic response of the hgprt locus. Of the drugs which were examined, VM-26, VP16-213, chlorambucil, mitomycin C, and cis-diamminedichloroplatinum(II) showed a particularly strong response in both of these assay systems. In terms of the minimum concentration which gave a mutagenic response, the drugs differed from each other by a factor of about 100,000, with actinomycin D, VM-26, and daunomycin being mutagenic in the range of 3 x 10(-8) to 1 x 10(-7) M, whereas dacarbazine produced a weak mutagenic response only at about 2 x 10(-3) M.
已在中国仓鼠卵巢细胞的两种不同检测系统中测定了13种抗肿瘤药物的诱变反应，这13种药物分别是苯丁酸氮芥、白消安、洛莫司汀、达卡巴嗪、阿霉素、柔红霉素、博来霉素、VM - 26、VP16 - 213、椭圆玫瑰树碱、放线菌素D、丝裂霉素C和顺二氯二氨铂（II）。这两种检测系统可测量多个基因位点的突变诱导情况以及姐妹染色单体交换频率。已测定反应的五个基因位点包括赋予对6 - 硫鸟嘌呤（Thgr或TGr）、哇巴因、吐根碱、甲基乙二醛双（胍腙）和5,6 - 二氯呋喃核糖基苯并咪唑抗性的位点；其中，只有Thgr标记影响一种对细胞生长并非必需的功能（次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶，hgprt位点）。所有这些药物在hgprt位点的突变频率均呈现剂量依赖性增加，但它们在其他基因位点的反应差异很大，并对不同化学类别的药物表现出明显的特异性。观察到的这些药物在基因位点特异性反应上的差异表明，它们在对不同染色体区域的可及性或亲和力方面可能存在差异。所有这些药物还导致姐妹染色单体交换频率显著增加，并且在姐妹染色单体交换检测中这些药物的活性与hgprt位点的诱变反应之间观察到非常好的相关性。在所检测的药物中，VM - 26、VP16 - 213、苯丁酸氮芥、丝裂霉素C和顺二氯二氨铂（II）在这两种检测系统中均表现出特别强烈的反应。就产生诱变反应的最低浓度而言，这些药物彼此相差约100,000倍，放线菌素D、VM - 26和柔红霉素在3×10⁻⁸至1×10⁻⁷M范围内具有诱变作用，而达卡巴嗪仅在约2×10⁻³M时产生微弱的诱变反应。
