MacPhee D G, Nagel B A, Podger D M
Mutat Res. 1983 Nov;111(3):283-93. doi: 10.1016/0027-5107(83)90027-1.
Ethionine, the ethyl analogue of methionine, slightly reduced the yield of reversions of the hisC3076 frameshift marker induced by 9-aminoacridine (9AA) in an excision-proficient strain of Salmonella typhimurium, but completely abolished mutagenesis by 9AA in the excision-deficient uvrB-deletion strain TA1537. No toxic effects of ethionine were apparent in either the excision-proficient or the excision-deficient strain. Because of the differential effects of ethionine on mutagenesis in the two strains, it seemed possible that an ethionine-sensitive step in the process(es) leading to fixation of 9AA-induced mutations might be compensated for by the uvrA,B,C+ excision-repair system. To further test this possibility, we used caffeine (a compound known to significantly reduce the efficacy of the excision-repair process) as a co-treatment with ethionine for cells of an excision-proficient strain exposed to 9AA. Treatment with caffeine alone or ethionine alone had very little effect on reversion yield, whereas co-treatment with the two agents abolished 9AA mutagenesis. It appeared, therefore, that either the caffeine-sensitive pathway or the ethionine-sensitive pathway needed to be functioning if 9AA-induced reversions of hisC3076 marker were to be detected. Addition of methionine to cells of the excision-deficient strain exposed to 9AA restored their ability to be mutated by 9AA, however. In a base-pair substitution back-mutation system, ethionine slightly enhanced the yields of revertants of the trpE8 marker induced by 2-aminopurine (2AP) in both an excision-proficient strain (at all 2AP dose levels tested) and an excision-deficient strain (only at the lower dose levels). In the excision-deficient strain, doses of 2AP above 300 micrograms/plate were highly toxic when ethionine was also present. It was for this reason that no 2AP-induced revertants were recovered at the higher 2AP concentrations. Treatment of the trpE8 strain with methionine also enhanced the yield of 2AP-induced revertants of this marker.
乙硫氨酸是甲硫氨酸的乙基类似物，在鼠伤寒沙门氏菌的一个切除功能正常的菌株中，它略微降低了由9 -氨基吖啶（9AA）诱导的hisC3076移码标记的回复突变率，但在切除缺陷的uvrB缺失菌株TA1537中，它完全消除了9AA的诱变作用。在切除功能正常或切除缺陷的菌株中，均未观察到乙硫氨酸的毒性作用。由于乙硫氨酸对两种菌株诱变作用的影响不同，导致9AA诱导突变固定的过程中，可能存在一个对乙硫氨酸敏感的步骤，而uvrA、B、C +切除修复系统可能对此起到了补偿作用。为了进一步验证这种可能性，我们使用咖啡因（一种已知能显著降低切除修复过程效率的化合物）与乙硫氨酸共同处理暴露于9AA的切除功能正常菌株的细胞。单独使用咖啡因或乙硫氨酸处理对回复突变率影响很小，而两种试剂共同处理则消除了9AA的诱变作用。因此，似乎如果要检测到9AA诱导的hisC3076标记的回复突变，咖啡因敏感途径或乙硫氨酸敏感途径必须发挥作用。然而，向暴露于9AA的切除缺陷菌株的细胞中添加甲硫氨酸，恢复了它们被9AA诱变的能力。在一个碱基对替换回复突变系统中，在切除功能正常的菌株（在所有测试的2 -氨基嘌呤（2AP）剂量水平下）和切除缺陷的菌株（仅在较低剂量水平下）中，乙硫氨酸均略微提高了由2AP诱导的trpE8标记的回复突变率。在切除缺陷的菌株中，当同时存在乙硫氨酸时，高于300微克/平板的2AP剂量具有高度毒性。正是由于这个原因，在较高的2AP浓度下未回收2AP诱导的回复突变体。用甲硫氨酸处理trpE8菌株也提高了该标记的2AP诱导的回复突变率。
