Postlabeling detection of DNA adducts of antitumor alkylating agents

1996 ◽  
Vol 38 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Guo-Hao Zhou ◽  
B. A. Teicher ◽  
Emil Frei III.
Keyword(s):  
Dna Adducts ◽  
Alkylating Agents ◽  
Antitumor Alkylating Agents

scholarly journals A ”Clickable” Probe for Active MGMT in Glioblastoma Demonstrates Two Discrete Populations of MGMT

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 453 ◽  
Author(s):  
Sudhir Raghavan ◽  
David S. Baskin ◽  
Martyn A. Sharpe
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Dna Adducts ◽  
Alkylating Agents ◽  
Chemotherapeutic Agents ◽  
Dna Alkylation ◽  
Methylated Dna ◽  
Methylguanine Methyltransferase ◽  
Discrete Populations

Various pathways can repair DNA alkylation by chemotherapeutic agents such as temozolomide (TMZ). The enzyme O6-methylguanine methyltransferase (MGMT) removes O6-methylated DNA adducts, leading to the failure of chemotherapy in resistant glioblastomas. Because of the anti-chemotherapeutic activities of MGMT previously described, estimating the levels of active MGMT in cancer cells can be a significant predictor of response to alkylating agents. Current methods to detect MGMT in cells are indirect, complicated, time-intensive, or utilize molecules that require complex and multistep chemistry synthesis. Our design simulates DNA repair by the transfer of a clickable propargyl group from O6-propargyl guanine to active MGMT and subsequent attachment of fluorescein-linked PEG linker via ”click chemistry.” Visualization of active MGMT levels reveals discrete active and inactive MGMT populations with biphasic kinetics for MGMT inactivation in response to TMZ-induced DNA damage.

Effect of hemoglobin solution on the response of intracranial and subcutaneous 9L tumors to antitumor alkylating agents

1993 ◽  
Vol 33 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Beverly A. Teicher ◽  
Sylvia A. Holden ◽  
Krishna Menon ◽  
Robert E. Hopkins ◽  
Maria S. Gawryl
Keyword(s):  
Alkylating Agents ◽  
Hemoglobin Solution ◽  
Antitumor Alkylating Agents

A new concentrated perfluorochemical emulsion and carbogen breathing as an adjuvant to treatment with antitumor alkylating agents

1992 ◽  
Vol 118 (7) ◽  
pp. 509-514 ◽  
Author(s):  
Beverly A. Teicher ◽  
Sylvia A. Holden ◽  
Gulshan Ara ◽  
Chul Soo Ha ◽  
Terence S. Herman ◽  
...  
Keyword(s):  
Alkylating Agents ◽  
Perfluorochemical Emulsion ◽  
Antitumor Alkylating Agents

scholarly journals Recent Studies on DNA Adducts Resulting from Human Exposure to Tobacco Smoke

Toxics ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 16 ◽  
Author(s):  
Bin Ma ◽  
Irina Stepanov ◽  
Stephen Hecht
Keyword(s):  
Dna Adducts ◽  
Analytical Methods ◽  
Alkylating Agents ◽  
Polycyclic Aromatic ◽  
Artifact Formation ◽  
Tobacco Specific Nitrosamines ◽  
Development And Validation ◽  
First Time

DNA adducts are believed to play a central role in the induction of cancer in cigarette smokers and are proposed as being potential biomarkers of cancer risk. We have summarized research conducted since 2012 on DNA adduct formation in smokers. A variety of DNA adducts derived from various classes of carcinogens, including aromatic amines, polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, alkylating agents, aldehydes, volatile carcinogens, as well as oxidative damage have been reported. The results are discussed with particular attention to the analytical methods used in those studies. Mass spectrometry-based methods that have higher selectivity and specificity compared to 32P-postlabeling or immunochemical approaches are preferred. Multiple DNA adducts specific to tobacco constituents have also been characterized for the first time in vitro or detected in vivo since 2012, and descriptions of those adducts are included. We also discuss common issues related to measuring DNA adducts in humans, including the development and validation of analytical methods and prevention of artifact formation.

scholarly journals Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma

2017 ◽  
Vol 18 (12) ◽  
pp. 917-926 ◽  
Author(s):  
R. J. Head ◽  
M. F. Fay ◽  
L. Cosgrove ◽  
K. Y. C. Fung ◽  
D. Rundle-Thiele ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Alkylating Agents ◽  
Cellular Resistance ◽  
Persistence Of Dna

Detection of Carcinogen–Macromolecular Adducts in Humans

1989 ◽  
Vol 8 (5) ◽  
pp. 913-932 ◽  
Author(s):  
A. Weston ◽  
D. K. Manchester ◽  
A. Povey ◽  
C. C. Harris
Keyword(s):  
Dna Adducts ◽  
Alkylating Agents ◽  
Dna Lesions ◽  
Target Cells ◽  
High Exposure ◽  
Increased Risk ◽  
Polycyclic Aromatic ◽  
Human Sera ◽  
Carcinogen Exposure ◽  
Risk Of Cancer

A major concern of molecular epidemiology is the identification of individuals at increased risk of cancer by obtaining evidence of high exposure to carcinogens that may lead to pathobiological lesions in target cells. DNA is considered to be a target for modification by mutagens and carcinogens; therefore, damage to DNA can be used as an internal, molecular dosimeter of carcinogen exposure. The reactive species of these carcinogens may bind either directly to DNA to form adducts or indirectly to cause secondary DNA lesions through free radicals and aldehydes. Highly sensitive and specific methods have been developed to measure DNA lesions and DNA repair products that are found in biological specimens from humans exposed to carcinogens in the environment. For example, DNA adducts have been measured in cells and tissues from people exposed environmentally to carcinogenic polycyclic aromatic hydrocarbons or alkylating agents. Antibodies recognizing carcinogen-DNA adducts have also been detected in human sera. Carcinogen-protein adducts are also being used as molecular dosimeters of carcinogen exposure. The advantages and limitations of the various methods used to measure carcinogen-macromolecular adducts are discussed here. The use of two or more complementary assays to obtain confirmatory results is recommended.

Sign in / Sign up

Export Citation Format

Share Document