DNA binding by [2,5-14C]N-nitrosopyrrolidine in excision-repair proficient and deficient strains of Salmonella. Evidence for a major premutagenic adduct.
DNA binding by [2,5-14C]N-nitrosopyrrolidine in excision-repair proficient and deficient strains of Salmonella. Evidence for a major premutagenic adduct.
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[2,5-14C]N-亚硝基吡咯烷在切除修复良好和缺陷的沙门氏菌菌株中与 DNA 结合。
DOI：
10.1093/carcin/9.10.1901
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发表时间：
1988
期刊：
影响因子：
4.7
通讯作者：
Guttenplan,JB
中科院分区：
文献类型：
--
作者：
Zielenska,M;Guttenplan,JB
Little is known about the nature and possible genotoxic effects of the DNA adducts formed byN-nitrosopyrrolidine (NPYR) in whole animals. DNA binding in DNA isolated from [2, 5-14C]NPYR-treatedSalmonellawas studied and attempts were made to monitor DNA adducts and correlated DNA binding with mutagenesis. NPYR was metabolized by hamster liver S-9 fraction in the presence ofS.typhimuriumTA1535 (uvrB−) or TA1975(uvrB+DNA isolated from TA1535 contained about three times as much radioactivity as that isolated from TA1975, and NPYR-induced mutagenesis was several-fold higher in TA1535. The fraction of radioactivity incorporated into TA1535 was ˜10-5. Thermal hydrolysis of the14C-containing DNA at neutral pH, followed by precipitation, released ˜2/3 of the radioactivity into the supernatant. HPLC analysis of the supernatant revealed one major peak. This peak was absent in DNA from TA1975. Acid hydrolysis of the DNA precipitate after neutral hydrolysis released most of the residual radioactivity. Several small peaks were observed after HPLC analysis of the TA1535 acid hydrolysate or the TA1975 acid hydrolysate. These results demonstrate that NPYR is capable of binding toSalmonellaDNA yielding one major product after hydrolysis and this DNA binding product appears to be repaired by the excision repair system. The fact that the major peak of radioactivity released fromSalmonellais only found in the strain which is efficiently reverted by NPYR suggests that mutagenesis is dependent on the DNA modification leading to this peak.
