Kopsidas G, MacPhee D G
School of Microbiology, La Trobe University, Melbourne, Victoria, Australia.
Mutat Res. 1996 Jun 10;352(1-2):135-42. doi: 10.1016/0027-5107(95)00216-2.
It has been shown that frameshift mutagenesis by 9-aminoacridine (9AA) in Salmonella typhimurium is significantly inhibited if glucose is present while cells are being treated in liquid defined medium. We suggested that this effect might be a result of glucose-provoked alterations of cAMP levels within the cell. We therefore sought to investigate the effects of exogenous cAMP on mutagenesis by 9-aminoacridine in both Salmonella typhimurium and Escherichia coli. Contrary to expectation, we found that frameshift mutagenesis was significantly depressed when high concentrations of cAMP were added to the defined medium during liquid treatment with 9AA. Other adenosine 5'-phosphates such as adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP) added to the liquid medium during 9AA treatment also substantially decreased the reversion rate to prototrophy in both S. typhimurium and E. coli, as did adenosine itself. Further experiments showed that neither influx nor efflux of 9-aminoacridine molecules were greatly affected by adenosine compounds, and that although cAMP and adenosine exerted similar antimutagenic effects on 9AA-treated stationary phase cells, their effects on log phase cells were quite different. The antimutagenic effect of a representative adenosine compound (ATP) was found to persist for some time after stationary phase cells had been washed, with maximal mutability being regained only after about 3 h.
研究表明，在鼠伤寒沙门氏菌中，如果在液体限定培养基中处理细胞时存在葡萄糖，9-氨基吖啶（9AA）引起的移码诱变会受到显著抑制。我们推测这种效应可能是细胞内葡萄糖引起的环磷酸腺苷（cAMP）水平变化的结果。因此，我们试图研究外源性cAMP对鼠伤寒沙门氏菌和大肠杆菌中9-氨基吖啶诱变的影响。与预期相反，我们发现，在用9AA进行液体处理期间，向限定培养基中添加高浓度的cAMP时，移码诱变显著降低。在9AA处理期间添加到液体培养基中的其他5'-磷酸腺苷，如三磷酸腺苷（ATP）、二磷酸腺苷（ADP）和一磷酸腺苷（AMP），以及腺苷本身，也显著降低了鼠伤寒沙门氏菌和大肠杆菌回复为原养型的频率。进一步的实验表明，9-氨基吖啶分子的流入和流出都没有受到腺苷化合物的很大影响，并且尽管cAMP和腺苷对9AA处理的稳定期细胞具有相似的抗诱变作用，但它们对对数期细胞的作用却大不相同。发现一种代表性的腺苷化合物（ATP）的抗诱变作用在稳定期细胞洗涤后会持续一段时间，只有在大约3小时后才会恢复到最大变异性。
