Analysis of the benzene oxide-DNA adduct 7-phenylguanine by liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry-parallel reaction monitoring: Application to DNA from exposed mice and humans

作者：Zarth Adam T; Cheng Guang; Zhang Zhaobin; Wang Mingyao; Villalta Peter W; Balbo Silvia; Hecht Stephen S^*

来源：Chemico-Biological Interactions, 2014, 215: 40-45.

DOI：10.1016/j.cbi.2014.03.002

• Benzene
• Benzene oxide
• 7-Phenylguanine
• DNA adducts
• Mass spectrometry

Benzene oxide, the initial metabolite of the human carcinogen benzene, reacts with DNA producing 7-phenylguanine (7-PhG) and other products. We developed a highly sensitive liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry-parallel reaction monitoring method for the analysis of 7-PhG in DNA. Accuracy and precision of the method were established and the detection limit was about 8 amol of 7-PhG injected on the column and less than 1 adduct per 109 nucleotides in DNA. 7-PhG was detected in calf thymus DNA reacted with 1 mu M to 10 mM benzene oxide. The method was applied for the analysis of DNA isolated from bone marrow, lung, and liver of B6C3F(1) mice treated by gavage with 50 mg/kg benzene in corn oil 5 times weekly for 4 weeks. 7-PhG was not detected in any of these DNA samples. The method was applied to DNA from mouse hepatocytes exposed to 100 mu M benzene oxide and human TK-6 lymphoblasts exposed to 100 mu M, 1, and 10 mM benzene oxide. 7-PhG was only detected in TK-6 cell DNA from the 10 mM exposure. The method was also applied to leukocyte DNA from 10 smokers and 10 nonsmokers. 7-PhG was detected in only one DNA sample, from a nonsmoker. The results of this study do not support the hypothesis that the benzene oxide-DNA adduct 7-PhG is involved in carcinogenesis by benzene.

• 出版日期2014-5-25