Role of fluorescence line-narrowing spectroscopy and related luminescence-based techniques in the elucidation of mechanisms of tumor initiation by polycyclic aromatic hydrocarbons and estrogens

Ryszard Jankowiak, Eleanor G Rogan, Ercole Cavalieri

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Formation of DNA adducts by various carcinogens represents the first critical event in the mechanism of tumor initiation. The carcinogenic polycyclic aromatic hydrocarbons (PAHs) are biologically activated by two major mechanisms: one-electron oxidation to produce radical cations and monooxygenation to form bay-region diol epoxides. The PAH-DNA adducts formed by these mechanisms are stable adducts that remain in DNA unless removed by repair and depurinating adducts that are lost from DNA by cleavage of the glycosyl bond. Identification of PAH-DNA adducts has relied heavily on low-temperature, laser-based fluorescence spectroscopy under non-line-narrowing (NLN) and line-narrowing (FLN) conditions. These spectroscopies can be used for chemical identification, conformational analysis, and/or probing the microenvironment of DNA (or protein) adducts. Small and co-workers have pioneered the use of FLN spectroscopy in this research. For example, the structures of the depurinating adducts formed by the PAHs benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and dibenzo[a,l]pyrene have been elucidated. Understanding of the mechanism of tumor initiation by PAHs has relied on identifying and quantifying the DNA adducts formed. The insights gained from the study of PAH-DNA adducts enabled us to discover the estrogen metabolites that form depurinating DNA adducts and can be potential endogenous initiators of human cancer. Small and co-workers have also studied the estrogen-DNA adducts and estrogen-thioether conjugates by using FLNS and related luminescence-based techniques and have demonstrated that the level of the 4-hydroxyestrone-l-N3-adenine depurinating adduct in breast tissue from a woman with breast carcinoma was significantly higher than that in breast tissue from women without breast cancer. The fluorescence- and phosphorescence-based techniques they are developing will be applied to analyzing estrogen adducts and conjugates as biomarkers of susceptibility to breast and other types of human cancer.

Original languageEnglish (US)
Pages (from-to)10266-10283
Number of pages18
JournalJournal of Physical Chemistry B
Volume108
Issue number29
DOIs
StatePublished - Jul 22 2004

Fingerprint

estrogens
DNA Adducts
Polycyclic Aromatic Hydrocarbons
polycyclic aromatic hydrocarbons
Polycyclic aromatic hydrocarbons
adducts
Luminescence
Tumors
Estrogens
tumors
Fluorescence
Spectroscopy
luminescence
fluorescence
deoxyribonucleic acid
spectroscopy
DNA
breast
Tissue
Pyrene

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

@article{f71e43fd1cdf4139a4961fdda19c2b92,
title = "Role of fluorescence line-narrowing spectroscopy and related luminescence-based techniques in the elucidation of mechanisms of tumor initiation by polycyclic aromatic hydrocarbons and estrogens",
abstract = "Formation of DNA adducts by various carcinogens represents the first critical event in the mechanism of tumor initiation. The carcinogenic polycyclic aromatic hydrocarbons (PAHs) are biologically activated by two major mechanisms: one-electron oxidation to produce radical cations and monooxygenation to form bay-region diol epoxides. The PAH-DNA adducts formed by these mechanisms are stable adducts that remain in DNA unless removed by repair and depurinating adducts that are lost from DNA by cleavage of the glycosyl bond. Identification of PAH-DNA adducts has relied heavily on low-temperature, laser-based fluorescence spectroscopy under non-line-narrowing (NLN) and line-narrowing (FLN) conditions. These spectroscopies can be used for chemical identification, conformational analysis, and/or probing the microenvironment of DNA (or protein) adducts. Small and co-workers have pioneered the use of FLN spectroscopy in this research. For example, the structures of the depurinating adducts formed by the PAHs benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and dibenzo[a,l]pyrene have been elucidated. Understanding of the mechanism of tumor initiation by PAHs has relied on identifying and quantifying the DNA adducts formed. The insights gained from the study of PAH-DNA adducts enabled us to discover the estrogen metabolites that form depurinating DNA adducts and can be potential endogenous initiators of human cancer. Small and co-workers have also studied the estrogen-DNA adducts and estrogen-thioether conjugates by using FLNS and related luminescence-based techniques and have demonstrated that the level of the 4-hydroxyestrone-l-N3-adenine depurinating adduct in breast tissue from a woman with breast carcinoma was significantly higher than that in breast tissue from women without breast cancer. The fluorescence- and phosphorescence-based techniques they are developing will be applied to analyzing estrogen adducts and conjugates as biomarkers of susceptibility to breast and other types of human cancer.",
author = "Ryszard Jankowiak and Rogan, {Eleanor G} and Ercole Cavalieri",
year = "2004",
month = "7",
day = "22",
doi = "10.1021/jp0402838",
language = "English (US)",
volume = "108",
pages = "10266--10283",
journal = "Journal of Physical Chemistry B Materials",
issn = "1520-6106",
publisher = "American Chemical Society",
number = "29",

}

TY - JOUR

T1 - Role of fluorescence line-narrowing spectroscopy and related luminescence-based techniques in the elucidation of mechanisms of tumor initiation by polycyclic aromatic hydrocarbons and estrogens

AU - Jankowiak, Ryszard

AU - Rogan, Eleanor G

AU - Cavalieri, Ercole

PY - 2004/7/22

Y1 - 2004/7/22

N2 - Formation of DNA adducts by various carcinogens represents the first critical event in the mechanism of tumor initiation. The carcinogenic polycyclic aromatic hydrocarbons (PAHs) are biologically activated by two major mechanisms: one-electron oxidation to produce radical cations and monooxygenation to form bay-region diol epoxides. The PAH-DNA adducts formed by these mechanisms are stable adducts that remain in DNA unless removed by repair and depurinating adducts that are lost from DNA by cleavage of the glycosyl bond. Identification of PAH-DNA adducts has relied heavily on low-temperature, laser-based fluorescence spectroscopy under non-line-narrowing (NLN) and line-narrowing (FLN) conditions. These spectroscopies can be used for chemical identification, conformational analysis, and/or probing the microenvironment of DNA (or protein) adducts. Small and co-workers have pioneered the use of FLN spectroscopy in this research. For example, the structures of the depurinating adducts formed by the PAHs benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and dibenzo[a,l]pyrene have been elucidated. Understanding of the mechanism of tumor initiation by PAHs has relied on identifying and quantifying the DNA adducts formed. The insights gained from the study of PAH-DNA adducts enabled us to discover the estrogen metabolites that form depurinating DNA adducts and can be potential endogenous initiators of human cancer. Small and co-workers have also studied the estrogen-DNA adducts and estrogen-thioether conjugates by using FLNS and related luminescence-based techniques and have demonstrated that the level of the 4-hydroxyestrone-l-N3-adenine depurinating adduct in breast tissue from a woman with breast carcinoma was significantly higher than that in breast tissue from women without breast cancer. The fluorescence- and phosphorescence-based techniques they are developing will be applied to analyzing estrogen adducts and conjugates as biomarkers of susceptibility to breast and other types of human cancer.

AB - Formation of DNA adducts by various carcinogens represents the first critical event in the mechanism of tumor initiation. The carcinogenic polycyclic aromatic hydrocarbons (PAHs) are biologically activated by two major mechanisms: one-electron oxidation to produce radical cations and monooxygenation to form bay-region diol epoxides. The PAH-DNA adducts formed by these mechanisms are stable adducts that remain in DNA unless removed by repair and depurinating adducts that are lost from DNA by cleavage of the glycosyl bond. Identification of PAH-DNA adducts has relied heavily on low-temperature, laser-based fluorescence spectroscopy under non-line-narrowing (NLN) and line-narrowing (FLN) conditions. These spectroscopies can be used for chemical identification, conformational analysis, and/or probing the microenvironment of DNA (or protein) adducts. Small and co-workers have pioneered the use of FLN spectroscopy in this research. For example, the structures of the depurinating adducts formed by the PAHs benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and dibenzo[a,l]pyrene have been elucidated. Understanding of the mechanism of tumor initiation by PAHs has relied on identifying and quantifying the DNA adducts formed. The insights gained from the study of PAH-DNA adducts enabled us to discover the estrogen metabolites that form depurinating DNA adducts and can be potential endogenous initiators of human cancer. Small and co-workers have also studied the estrogen-DNA adducts and estrogen-thioether conjugates by using FLNS and related luminescence-based techniques and have demonstrated that the level of the 4-hydroxyestrone-l-N3-adenine depurinating adduct in breast tissue from a woman with breast carcinoma was significantly higher than that in breast tissue from women without breast cancer. The fluorescence- and phosphorescence-based techniques they are developing will be applied to analyzing estrogen adducts and conjugates as biomarkers of susceptibility to breast and other types of human cancer.

UR - http://www.scopus.com/inward/record.url?scp=3442882501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3442882501&partnerID=8YFLogxK

U2 - 10.1021/jp0402838

DO - 10.1021/jp0402838

M3 - Article

VL - 108

SP - 10266

EP - 10283

JO - Journal of Physical Chemistry B Materials

JF - Journal of Physical Chemistry B Materials

SN - 1520-6106

IS - 29

ER -