Ferguson L R, Hill C L, Morecombe P
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
Eur J Cancer. 1992;28A(4-5):736-42. doi: 10.1016/0959-8049(92)90106-c.
A mutagenicity assay using AA8 Chinese hamster cells has been used to explore the potential of some currently used clinical anticancer drugs to induce cells resistant to 6-thioguanine and cytarabine. Preliminary experiments gave evidence of a "low dose" and "high dose" resistance to cytarabine, and subsequent work considered only the latter of these events. When ethyl methane sulphonate was used as a reference mutagen, induced resistance to cytarabine developed substantially later and at a lower frequency than resistance to 6-thioguanine. Of the clinical drugs tested, carmustine showed the highest ability to induce either 6-thioguanine or cytarabine resistant cells. Bleomycin, daunomycin and amsacrine showed moderate ability, while vincristine was essentially inactive in these assays. Such information could potentially be used in selecting new drug combinations or timing of drug administration in cancer chemotherapy.
利用AA8中国仓鼠细胞进行的致突变性试验,已用于探究一些目前使用的临床抗癌药物诱导细胞对6-硫鸟嘌呤和阿糖胞苷产生抗性的可能性。初步实验证明了对阿糖胞苷存在“低剂量”和“高剂量”抗性,后续工作仅考虑了这些情况中的后者。当使用甲磺酸乙酯作为参考诱变剂时,诱导产生的对阿糖胞苷的抗性比6-硫鸟嘌呤抗性出现得晚得多,且频率更低。在所测试的临床药物中,卡莫司汀诱导产生6-硫鸟嘌呤或阿糖胞苷抗性细胞的能力最强。博来霉素、柔红霉素和安吖啶表现出中等能力,而长春新碱在这些试验中基本无活性。此类信息可能有助于在癌症化疗中选择新的药物组合或确定给药时间。