The Resource Nitrosation studies of tolazoline, an antihypertensive drug and LC/MS detection of DNA adducts derived from N-nitrosotolazoline, by Jianzheng Shi

Nitrosation studies of tolazoline, an antihypertensive drug and LC/MS detection of DNA adducts derived from N-nitrosotolazoline, by Jianzheng Shi

Label
Nitrosation studies of tolazoline, an antihypertensive drug and LC/MS detection of DNA adducts derived from N-nitrosotolazoline
Title
Nitrosation studies of tolazoline, an antihypertensive drug and LC/MS detection of DNA adducts derived from N-nitrosotolazoline
Statement of responsibility
by Jianzheng Shi
Creator
Subject
Language
eng
Summary
Nitrosation of tolazoline, the simplest one in the family of imidazoline-based drugs led a variety of products, including nitrosamines, nitrosamides and diazonium ions derived compounds. This transformation was perceived to occur through the nitrous acid addition across the C=N double bond, followed by decomposition of the resulting Ü-hydroxynitrosamines. The rapid nitrosation of tolazoline along with the generation of diazonium ions derived products without the aid of enzymes could have health significance. This health significance was investigated through the chemistry of N-nitroso-tolazoline, the key intermediate in the nitrosation of tolazoline. N-nitrosotolazoline was unstable under weak acidic conditions and decomposed to diazonium ions, which were eventually trapped by water or other nucleophiles. This decomposition was general acid catalyzed reaction and N-acetylcysteine could not effectively block the formation of diazonium ions. The potential DNA adducts was elucidated through the reaction of 2 ' -deoxyguanosine and 2 ' -deoxyadenosine with N-nitrosotolazoline. All the N and O atoms in guanine and adenine bases could be alkylated by the diazonium ions derived from the decomposition of N-nitrosotolazoline. Major adducts have been prepared independently through chemical synthesis and used as authentic standards for the quantitative analysis of DNA adducts. When double strand calf-thymus DNA was incubated with N-nitrosotolazoline, two guanine base adducts and two adenine base adducts were quantitatively analyzed by LGMS with MRM methods. The maximum adducts level was 60 adducts/10 4 guanine base. This result suggests further experiments on animal are needed for the evaluation of the genetic toxicity of this imidazoline-based drug
Additional physical form
Also available on the Internet.
Cataloging source
MUU
http://library.link/vocab/creatorDate
1968-
http://library.link/vocab/creatorName
Shi, Jianzheng
Degree
Ph. D.
Dissertation year
2002.
Government publication
government publication of a state province territory dependency etc
Granting institution
University of Missouri-Columbia
Illustrations
illustrations
Index
no index present
Literary form
non fiction
Nature of contents
  • bibliography
  • theses
http://library.link/vocab/subjectName
  • Imidazolines
  • Nitrosation
  • Drugs
  • Genetic toxicology
  • Hypotensive agents
Target audience
specialized
Label
Nitrosation studies of tolazoline, an antihypertensive drug and LC/MS detection of DNA adducts derived from N-nitrosotolazoline, by Jianzheng Shi
Instantiates
Publication
Note
  • Typescript
  • Vita
Bibliography note
Includes bibliographical references (leaves 164-173)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Control code
52598907
Dimensions
29 cm
Dimensions
unknown
Extent
xii, 174 leaves
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Other physical details
illustrations
Specific material designation
remote
Label
Nitrosation studies of tolazoline, an antihypertensive drug and LC/MS detection of DNA adducts derived from N-nitrosotolazoline, by Jianzheng Shi
Publication
Note
  • Typescript
  • Vita
Bibliography note
Includes bibliographical references (leaves 164-173)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Control code
52598907
Dimensions
29 cm
Dimensions
unknown
Extent
xii, 174 leaves
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Other physical details
illustrations
Specific material designation
remote

Library Locations

    • University of Missouri Libraries DepositoryBorrow it
      2908 Lemone Blvd, Columbia, MO, 65211, US
      38.919360 -92.291620
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