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Biomonitoring Exposures to Environmental and Dietary Carcinogens by Targeted and Untargeted Mass Spectrometry- [electronic resource]
Biomonitoring Exposures to Environmental and Dietary Carcinogens by Targeted and Untargete...
Biomonitoring Exposures to Environmental and Dietary Carcinogens by Targeted and Untargeted Mass Spectrometry- [electronic resource]

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자료유형  
 학위논문파일 국외
최종처리일시  
20240214095924
ISBN  
9798380123761
DDC  
543
저자명  
Konorev, Dmitri.
서명/저자  
Biomonitoring Exposures to Environmental and Dietary Carcinogens by Targeted and Untargeted Mass Spectrometry - [electronic resource]
발행사항  
[S.l.]: : University of Minnesota., 2022
발행사항  
Ann Arbor : : ProQuest Dissertations & Theses,, 2022
형태사항  
1 online resource(198 p.)
주기사항  
Source: Dissertations Abstracts International, Volume: 85-02, Section: B.
주기사항  
Advisor: Turesky, Robert J.;Peterson, Lisa A.
학위논문주기  
Thesis (Ph.D.)--University of Minnesota, 2022.
사용제한주기  
This item must not be sold to any third party vendors.
초록/해제  
요약Humans are exposed to a wide variety of exogenous chemicals that may be implicated in DNA damage and cancer. Typical sources of carcinogen exposure include the diet, environment, and tobacco smoke. There is an epidemiological link between smoking cancer, as well as cooked and red meat consumption, and cancer. Despite extensive study, the chemicals responsible for carcinogenesis are unconfirmed. Specific and sensitive markers of DNA damage by discrete chemicals are needed confirm existing paradigms of carcinogenesis. Chapter 1 outlines the epidemiology and mechanisms by which chemicals from the diet and tobacco can lead to colorectal cancer and bladder cancer.Tobacco smoking is a well-established cause of bladder cancer, as is occupational exposure to high levels of carcinogenic aromatic amines, such as 4-aminobiphenyl and 2-naphthylamine, which are also present in tobacco smoke at low levels. The levels of these compounds in tobacco smoke may be insufficient to bladder carcinogenesis. Other related compounds, such as alkylaniline derivatives, and structurally-related heterocyclic aromatic amines, are present at much higher levels in tobacco smoke and may be risk factors for bladder cancer. Chapter 2 outlines our methodologies to assay a nonpolar, basic fraction of tobacco smoke condensate, containing aromatic amines and heterocyclic aromatic amines, by liquid chromatography coupled to mass spectrometry (LC/MS). These compounds were measured by targeted and untargeted LC/MS as well as with the use of high field asymmetric waveform ion mobility spectrometry coupled to LC/MS to add an additional dimension of separation and reduce sample complexity.Chapter 3 presents our original research in the development of highly sensitive, validated LC/MS methods to measure DNA adducts and abasic sites from cooked meat and tobacco carcinogens in colorectal tissue. These methods were developed using a rat animal model dosed with carcinogens that form DNA adducts associated with colorectal cancer based on previous epidemiological and mechanistic evidence. In Chapter 4, we applied this methodology to human colorectal DNA samples from colorectal cancer patient biopsy samples. We did not detect DNA adducts of exogenous carcinogens but did detect endogenously-formed DNA and abasic sites in these samples. We then contextualized these results within greater paradigms of colorectal cancer carcinogenesis.
일반주제명  
Analytical chemistry.
일반주제명  
Chemistry.
일반주제명  
Toxicology.
일반주제명  
Oncology.
키워드  
DNA adducts
키워드  
FAIMS
키워드  
LC/MS
키워드  
Mass spectrometry
키워드  
Tobacco carcinogens
기타저자  
University of Minnesota Medicinal Chemistry
기본자료저록  
Dissertations Abstracts International. 85-02B.
기본자료저록  
Dissertation Abstract International
전자적 위치 및 접속  
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MARC

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■035    ▼a(MiAaPQ)AAI29321546
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a543
■1001  ▼aKonorev,  Dmitri.
■24510▼aBiomonitoring  Exposures  to  Environmental  and  Dietary  Carcinogens  by  Targeted  and  Untargeted  Mass  Spectrometry▼h[electronic  resource]
■260    ▼a[S.l.]:▼bUniversity  of  Minnesota.  ▼c2022
■260  1▼aAnn  Arbor  :▼bProQuest  Dissertations  &  Theses,  ▼c2022
■300    ▼a1  online  resource(198  p.)
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-02,  Section:  B.
■500    ▼aAdvisor:  Turesky,  Robert  J.;Peterson,  Lisa  A.
■5021  ▼aThesis  (Ph.D.)--University  of  Minnesota,  2022.
■506    ▼aThis  item  must  not  be  sold  to  any  third  party  vendors.
■520    ▼aHumans  are  exposed  to  a  wide  variety  of  exogenous  chemicals  that  may  be  implicated  in  DNA  damage  and  cancer.  Typical  sources  of  carcinogen  exposure  include  the  diet,  environment,  and  tobacco  smoke.  There  is  an  epidemiological  link  between  smoking  cancer,  as  well  as  cooked  and  red  meat  consumption,  and  cancer.  Despite  extensive  study,  the  chemicals  responsible  for  carcinogenesis  are  unconfirmed.  Specific  and  sensitive  markers  of  DNA  damage  by  discrete  chemicals  are  needed  confirm  existing  paradigms  of  carcinogenesis.  Chapter  1  outlines  the  epidemiology  and  mechanisms  by  which  chemicals  from  the  diet  and  tobacco  can  lead  to  colorectal  cancer  and  bladder  cancer.Tobacco  smoking  is  a  well-established  cause  of  bladder  cancer,  as  is  occupational  exposure  to  high  levels  of  carcinogenic  aromatic  amines,  such  as  4-aminobiphenyl  and  2-naphthylamine,  which  are  also  present  in  tobacco  smoke  at  low  levels.  The  levels  of  these  compounds  in  tobacco  smoke  may  be  insufficient  to  bladder  carcinogenesis.  Other  related  compounds,  such  as  alkylaniline  derivatives,  and  structurally-related  heterocyclic  aromatic  amines,  are  present  at  much  higher  levels  in  tobacco  smoke  and  may  be  risk  factors  for  bladder  cancer.  Chapter  2  outlines  our  methodologies  to  assay  a  nonpolar,  basic  fraction  of  tobacco  smoke  condensate,  containing  aromatic  amines  and  heterocyclic  aromatic  amines,  by  liquid  chromatography  coupled  to  mass  spectrometry  (LC/MS).  These  compounds  were  measured  by  targeted  and  untargeted  LC/MS  as  well  as  with  the  use  of  high  field  asymmetric  waveform  ion  mobility  spectrometry  coupled  to  LC/MS  to  add  an  additional  dimension  of  separation  and  reduce  sample  complexity.Chapter  3  presents  our  original  research  in  the  development  of  highly  sensitive,  validated  LC/MS  methods  to  measure  DNA  adducts  and  abasic  sites  from  cooked  meat  and  tobacco  carcinogens  in  colorectal  tissue.  These  methods  were  developed  using  a  rat  animal  model  dosed  with  carcinogens  that  form  DNA  adducts  associated  with  colorectal  cancer  based  on  previous  epidemiological  and  mechanistic  evidence.  In  Chapter  4,  we  applied  this  methodology  to  human  colorectal  DNA  samples  from  colorectal  cancer  patient  biopsy  samples.  We  did  not  detect  DNA  adducts  of  exogenous  carcinogens  but  did  detect  endogenously-formed  DNA  and  abasic  sites  in  these  samples.  We  then  contextualized  these  results  within  greater  paradigms  of  colorectal  cancer  carcinogenesis.
■590    ▼aSchool  code:  0130.
■650  4▼aAnalytical  chemistry.
■650  4▼aChemistry.
■650  4▼aToxicology.
■650  4▼aOncology.
■653    ▼aDNA  adducts
■653    ▼aFAIMS
■653    ▼aLC/MS
■653    ▼aMass  spectrometry
■653    ▼aTobacco  carcinogens
■690    ▼a0486
■690    ▼a0485
■690    ▼a0383
■690    ▼a0992
■71020▼aUniversity  of  Minnesota▼bMedicinal  Chemistry.
■7730  ▼tDissertations  Abstracts  International▼g85-02B.
■773    ▼tDissertation  Abstract  International
■790    ▼a0130
■791    ▼aPh.D.
■792    ▼a2022
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16931134▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.
■980    ▼a202402▼f2024

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