Antimutagenic effects of 2(3)-tert-butyl-4-hydroxyanisole and of antimicrobial agents.
Antimutagenic effects of 2(3)-tert-butyl-4-hydroxyanisole and of antimicrobial agents.
复制标题
2(3)-叔丁基-4-羟基苯甲醚和抗菌剂的抗突变作用。
作者：
R. Batzinger;S. L. Ou;E. Bueding
在饮食中加入抗氧化剂2(3)-叔丁基-4-羟基异醇（BHA）和乙氧基喹啉（1,2-二氢-6-乙氧基-2,2,4-三甲基喹啉），可以显著降低苯并(a)芘处理小鼠体内的诱变剂水平。这反映在宿主介导的实验结果和尿液诱变活性的测定中，使用的是Ames及其同事开发的鼠伤寒沙门菌TA100和TA98敏感测试菌株。用丁基羟基茴香醚治疗也能有效降低海坎酮、其他三种抗血吸虫化合物、甲硝唑、地西泮和甲苯达唑的体内致突变活性。这些影响伴随着某些组织中硫醇含量的增加。另外两种抗血吸虫药物（4-异硫氰基-4'-硝基二苯胺和奥胺喹）的致突变代谢物的产生并未因BHA治疗而减少。然而，这种致突变性的降低可以通过肠道抗菌药物的施用来实现，这意味着肠道微生物在某些化学药物的致突变性激活中的作用。BHA和肠道抗菌剂联合治疗小鼠，使甲硝唑衍生的诱变剂水平降低了90%以上，联合治疗比单独治疗更有效。
Administration of the antioxidants 2(3)-tert-butyl-4-hydroxyanisole (BHA) and ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) with the diet resulted in a marked decrease in the levels of mutagens present in mice treated with benzo(a)pyrene. This was reflected in the results of the host-mediated assay and determinations of the mutagenic activities of the urine, with the use of the sensitive tester strains TA100 and TA98 of Salmonella typhimurium his- developed by Ames and coworkers. Treatment with BHA was effective also in reducing the mutagenic activities in vivo of hycanthone, three other antischistosomal compounds, metronidazole, diazepam, and mebendazole. These effects were accompanied by increases in the thiol levels of some tissues. The production of mutagenic metabolites of two other antischistosomal drugs, 4-isothiocyano-4'-nitrodiphenylamine and oxamniquine, was not reduced by BHA treatment. However, such reductions in mutagenicity could be achieved by the administration of enteric antibacterial agents, implicating the role of intestinal microorganisms in the mutagenic activation of certain chemical agents. Combined treatment of mice with BHA and enteric antimicrobial agents reduced the levels of mutagens derived from metronidazole by more than 90%, and the combined treatments were more effective than was either treatment alone.