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Studies of carcinogen-modified DNA a...
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Li, Linge.
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Studies of carcinogen-modified DNA adducts by high performance liquid chromatography and mass spectrometry.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Studies of carcinogen-modified DNA adducts by high performance liquid chromatography and mass spectrometry./
作者:
Li, Linge.
面頁冊數:
148 p.
附註:
Adviser: M. Paul Chiarelli.
Contained By:
Dissertation Abstracts International64-03B.
標題:
Chemistry, Analytical. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3085090
Studies of carcinogen-modified DNA adducts by high performance liquid chromatography and mass spectrometry.
Li, Linge.
Studies of carcinogen-modified DNA adducts by high performance liquid chromatography and mass spectrometry.
- 148 p.
Adviser: M. Paul Chiarelli.
Thesis (Ph.D.)--Loyola University of Chicago, 2003.
This dissertation describes different analytical approaches for the detection and structural differentiation of aromatic carcinogen-modified DNA using mass spectrometry. Separation, detection and quantitation of aromatic-modified DNA adducts were carried out using micro-HPLC/UV spectrometry and nano-LC/ESI ion trap mass spectrometry. An on-line method of solid-phase extraction (SPE) followed by HPLC was developed to isolate ultra trace amount of DNA adducts from large quantities of normal DNA. This method was accomplished by coupling micro-HPLC with a valve-switching technique. The detection of aromatic-modified DNA adducts at ∼1 fmol (10<super>−15</super> mole) quantity using SIM and SRM detection modes was demonstrated using an ion trap mass spectrometry coupled with nano-electrospray ionization. In addition, a linear correlation between the signal intensity and the amount of analyte injected was established in the range of 1.5 fmol to 168 fmol quantity, suggesting quantification for aromatic-modified DNA adducts may be achieved on nano-LC/ESI/MS. Moreover, the analysis of a DNA adduct mixture, even in the presence of large excess of normal deoxynucleosides (in a DNA digest), was successfully demonstrated on the nano-LC/ESI ion trap mass spectrometry.Subjects--Topical Terms:
586156
Chemistry, Analytical.
Studies of carcinogen-modified DNA adducts by high performance liquid chromatography and mass spectrometry.
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This dissertation describes different analytical approaches for the detection and structural differentiation of aromatic carcinogen-modified DNA using mass spectrometry. Separation, detection and quantitation of aromatic-modified DNA adducts were carried out using micro-HPLC/UV spectrometry and nano-LC/ESI ion trap mass spectrometry. An on-line method of solid-phase extraction (SPE) followed by HPLC was developed to isolate ultra trace amount of DNA adducts from large quantities of normal DNA. This method was accomplished by coupling micro-HPLC with a valve-switching technique. The detection of aromatic-modified DNA adducts at ∼1 fmol (10<super>−15</super> mole) quantity using SIM and SRM detection modes was demonstrated using an ion trap mass spectrometry coupled with nano-electrospray ionization. In addition, a linear correlation between the signal intensity and the amount of analyte injected was established in the range of 1.5 fmol to 168 fmol quantity, suggesting quantification for aromatic-modified DNA adducts may be achieved on nano-LC/ESI/MS. Moreover, the analysis of a DNA adduct mixture, even in the presence of large excess of normal deoxynucleosides (in a DNA digest), was successfully demonstrated on the nano-LC/ESI ion trap mass spectrometry.
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The structural characterization and differentiation of carcinogen-modified DNA adducts was accomplished by tandem mass spectrometry (MS/MS). The product ion formation characteristics of thirteen different C8-substituted alkylaniline adducts of guanine were studied using ESI quadrupole ion trap tandem mass spectrometry. A similarity index (SI) was used to differentiate the structures of isomers. The structures of all isomeric BH<sub>2</sub><super>+</super> ions studied here could be differentiated based on the calculation of the similarity index using five or six product ions. The product ion spectra acquired over a two month period with the ion trap were found to be sufficiently reproducible to give almost identical Sls for these DNA adducts as well. These results suggest that a searchable database of product ion spectra may be created and used to identify unknown guanine adducts when they are detected with structural information. (Abstract shortened by UMI.)
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