Mutation and formation of methyl- and hydroxylguanine adducts in DNA caused by N-nitrosodimethylamine and N-nitrosodiethylamine with UVA irradiation.
Mutation and formation of methyl- and hydroxylguanine adducts in DNA caused by N-nitrosodimethylamine and N-nitrosodiethylamine with UVA irradiation.
复制标题
UVA 照射下 N-亚硝基二甲胺和 N-亚硝基二乙胺引起 DNA 中甲基和羟基鸟嘌呤加合物的突变和形成。
作者：
S. Arimoto;Keiko Kaji;G. Sweetman;H. Hayatsu
以前，我们报道，当大肠杆菌处理N-亚硝基二烷基胺在近紫外光照射下，诱变的细菌发生：有没有代谢活化的要求。我们现在已经研究了由N-亚硝基二甲胺（NDMA）和N-亚硝基二乙胺（NDEA）与UVA（320-400 nm）照射引起的突变光谱，使用标准试验菌株鉴定突变类型。NDMA + UVA诱发的突变为转换GC->AT和颠换GC->CG、GC->TA和AT->TA。NDEA + UVA主要诱导GC->CG的颠换。在这两种情况下，均未观察到移码突变。O_6-烷基鸟嘌呤-DNA烷基转移酶缺陷型E.大肠杆菌和鼠伤寒沙门氏菌，NDMA + UVA和NDEA + UVA的突变水平变得显著高于用熟练菌株观察到的那些。我们测量了NDMA + UVA处理的小牛胸腺DNA中O 6-甲基鸟嘌呤（O 6-meG）水平。O 6-meG水平增加作为NDMA浓度和照射时间的函数。我们还在用NDMA + UVA处理的DNA中检测到N7-甲基鸟嘌呤。在我们以前的工作中，我们发现了8-oxodG的形成在DNA处理N-亚硝基吗啉+ UVA。经NDMA + UVA处理的DNA中的8-oxodG/dG比率比未经处理的对照增加高达42倍，并且经NDEA + UVA处理的DNA中的8-oxodG/dG比率增加高达67倍。8-OxodG的形成不受影响，通过用D2 O替换反应混合物中的H2O，这表明单线态氧不是该光活化中的速率限制因素。我们的结论是，烷基化和氧化参与了NDMA + UVA和NDEA + UVA诱导的突变。
Previously we reported that when Escherichia coli was treated with N-nitrosodialkylamine under irradiation with near UV light, mutagenesis of the bacteria took place: there was no requirement for metabolic activation. We have now studied the spectra of mutations caused by N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) with UVA (320-400 nm) irradiation, using standard tester strains for identifying types of mutations. Induced mutations by NDMA + UVA were the transition GC-->AT and transversions GC-->CG, GC-->TA and AT-->TA. NDEA + UVA induced mainly the GC-->CG transversion. In both cases no frameshift mutations were observed. When O6-alkylguanine-DNA alkyltransferase-deficient strains of E. coli and Salmonella typhimurium were used, the mutation levels with both NDMA + UVA and NDEA + UVA became remarkably higher than those observed with the proficient strains. We measured the O6-methylguanine (O6-meG) level in calf thymus DNA treated with NDMA + UVA. The O6-meG level was increased as a function of NDMA concentration and irradiation time. We also detected N7-methylguanine in DNA treated with NDMA + UVA. In our previous work we found formation of 8-oxodeoxyguanosine (8-oxodG) in DNA treated with N-nitrosomorpholine + UVA. The 8-oxodG/dG ratio in DNA treated with NDMA + UVA increased up to 42-fold over that of the untreated control and that in DNA treated with NDEA + UVA increased up to 67-fold. 8-OxodG formation was not affected by replacing H2O in the reaction mixture with D2O, suggesting that singlet oxygen is not the rate limiting factor in this photoactivation. We conclude that both alkylation and oxidation are involved in mutations induced by NDMA + UVA and NDEA + UVA.
影响因子：
5.9
作者：
YANG, CS;YOO, JSH;HONG, JY
通讯作者：
HONG, JY
影响因子：
2.9
作者：
WOOD, ML;DIZDAROGLU, M;ESSIGMANN, JM
通讯作者：
ESSIGMANN, JM
DOI：
10.1073/pnas.81.20.6271
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LOECHLER, EL;GREEN, CL;ESSIGMANN, JM
通讯作者：
ESSIGMANN, JM