Formation of DNA adducts in HL-60 cells treated with the toluene metabolite p-cresol

A potential biomarker for toluene exposure

Nilesh W. Gaikwad, William J. Bodell

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We have examined DNA adduct formation in myeloperoxidase containing HL-60 cells treated with the toluene metabolite p-cresol. Treatment of HL-60 cells with the combination of p-cresol and H2O2 produced four DNA adducts 1: (75.0%), 2: (9.1%), 3: (7.0%) and 4: (8.8%) and adduct levels ranging from 0.3 to 33.6×10-7. The levels of DNA adducts formed by p-cresol were dependent on concentrations of p-cresol, H2O2 and treatment time. In vitro incubation of p-cresol with myeloperoxidase and H2O2 produced three DNA adducts 1: (40.5%), 2: (28.4%) and 3: (29.7%) with a relative adduct level of 0.7×10-7. The quinone methide derivative of p-cresol (PCQM) was prepared by Ag(I)O oxidation. Reaction of calf thymus DNA with PCQM produced four adducts 1: (18.5%), 2: (36.4%), 3: (29.0%) and 5: (16.0%) with a relative adduct level 1.6×10-7. Rechromatography analyses indicates that DNA adducts 1-3 formed in HL-60 cells treated with p-cresol and after myeloperoxidase activation of p-cresol were similar to those formed by reaction of DNA with PCQM. This observation suggests that p-cresol is activated to a quinone methide intermediate in each of these activation systems. Taken together, these results suggest PCQM is the reactive intermediate leading to the formation of DNA adducts in HL-60 cells treated with p-cresol. Furthermore, the DNA adducts formed by PCQM may provide a biomarker to assess occupational exposure to toluene.

Original languageEnglish (US)
Pages (from-to)149-158
Number of pages10
JournalChemico-Biological Interactions
Volume145
Issue number2
DOIs
StatePublished - May 6 2003

Fingerprint

DNA Adducts
HL-60 Cells
Toluene
Biomarkers
Metabolites
Peroxidase
Chemical activation
4-cresol
Occupational Exposure
Derivatives
Oxidation

Keywords

  • DNA adducts
  • HL-60 cells
  • Myeloperoxidase
  • p-Cresol
  • Toluene

ASJC Scopus subject areas

  • Toxicology

Cite this

Formation of DNA adducts in HL-60 cells treated with the toluene metabolite p-cresol : A potential biomarker for toluene exposure. / Gaikwad, Nilesh W.; Bodell, William J.

In: Chemico-Biological Interactions, Vol. 145, No. 2, 06.05.2003, p. 149-158.

Research output: Contribution to journalArticle

@article{e2820f4e6b6745f7b9963b693598aac7,
title = "Formation of DNA adducts in HL-60 cells treated with the toluene metabolite p-cresol: A potential biomarker for toluene exposure",
abstract = "We have examined DNA adduct formation in myeloperoxidase containing HL-60 cells treated with the toluene metabolite p-cresol. Treatment of HL-60 cells with the combination of p-cresol and H2O2 produced four DNA adducts 1: (75.0{\%}), 2: (9.1{\%}), 3: (7.0{\%}) and 4: (8.8{\%}) and adduct levels ranging from 0.3 to 33.6×10-7. The levels of DNA adducts formed by p-cresol were dependent on concentrations of p-cresol, H2O2 and treatment time. In vitro incubation of p-cresol with myeloperoxidase and H2O2 produced three DNA adducts 1: (40.5{\%}), 2: (28.4{\%}) and 3: (29.7{\%}) with a relative adduct level of 0.7×10-7. The quinone methide derivative of p-cresol (PCQM) was prepared by Ag(I)O oxidation. Reaction of calf thymus DNA with PCQM produced four adducts 1: (18.5{\%}), 2: (36.4{\%}), 3: (29.0{\%}) and 5: (16.0{\%}) with a relative adduct level 1.6×10-7. Rechromatography analyses indicates that DNA adducts 1-3 formed in HL-60 cells treated with p-cresol and after myeloperoxidase activation of p-cresol were similar to those formed by reaction of DNA with PCQM. This observation suggests that p-cresol is activated to a quinone methide intermediate in each of these activation systems. Taken together, these results suggest PCQM is the reactive intermediate leading to the formation of DNA adducts in HL-60 cells treated with p-cresol. Furthermore, the DNA adducts formed by PCQM may provide a biomarker to assess occupational exposure to toluene.",
keywords = "DNA adducts, HL-60 cells, Myeloperoxidase, p-Cresol, Toluene",
author = "Gaikwad, {Nilesh W.} and Bodell, {William J.}",
year = "2003",
month = "5",
day = "6",
doi = "10.1016/S0009-2797(02)00249-1",
language = "English (US)",
volume = "145",
pages = "149--158",
journal = "Chemico-Biological Interactions",
issn = "0009-2797",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Formation of DNA adducts in HL-60 cells treated with the toluene metabolite p-cresol

T2 - A potential biomarker for toluene exposure

AU - Gaikwad, Nilesh W.

AU - Bodell, William J.

PY - 2003/5/6

Y1 - 2003/5/6

N2 - We have examined DNA adduct formation in myeloperoxidase containing HL-60 cells treated with the toluene metabolite p-cresol. Treatment of HL-60 cells with the combination of p-cresol and H2O2 produced four DNA adducts 1: (75.0%), 2: (9.1%), 3: (7.0%) and 4: (8.8%) and adduct levels ranging from 0.3 to 33.6×10-7. The levels of DNA adducts formed by p-cresol were dependent on concentrations of p-cresol, H2O2 and treatment time. In vitro incubation of p-cresol with myeloperoxidase and H2O2 produced three DNA adducts 1: (40.5%), 2: (28.4%) and 3: (29.7%) with a relative adduct level of 0.7×10-7. The quinone methide derivative of p-cresol (PCQM) was prepared by Ag(I)O oxidation. Reaction of calf thymus DNA with PCQM produced four adducts 1: (18.5%), 2: (36.4%), 3: (29.0%) and 5: (16.0%) with a relative adduct level 1.6×10-7. Rechromatography analyses indicates that DNA adducts 1-3 formed in HL-60 cells treated with p-cresol and after myeloperoxidase activation of p-cresol were similar to those formed by reaction of DNA with PCQM. This observation suggests that p-cresol is activated to a quinone methide intermediate in each of these activation systems. Taken together, these results suggest PCQM is the reactive intermediate leading to the formation of DNA adducts in HL-60 cells treated with p-cresol. Furthermore, the DNA adducts formed by PCQM may provide a biomarker to assess occupational exposure to toluene.

AB - We have examined DNA adduct formation in myeloperoxidase containing HL-60 cells treated with the toluene metabolite p-cresol. Treatment of HL-60 cells with the combination of p-cresol and H2O2 produced four DNA adducts 1: (75.0%), 2: (9.1%), 3: (7.0%) and 4: (8.8%) and adduct levels ranging from 0.3 to 33.6×10-7. The levels of DNA adducts formed by p-cresol were dependent on concentrations of p-cresol, H2O2 and treatment time. In vitro incubation of p-cresol with myeloperoxidase and H2O2 produced three DNA adducts 1: (40.5%), 2: (28.4%) and 3: (29.7%) with a relative adduct level of 0.7×10-7. The quinone methide derivative of p-cresol (PCQM) was prepared by Ag(I)O oxidation. Reaction of calf thymus DNA with PCQM produced four adducts 1: (18.5%), 2: (36.4%), 3: (29.0%) and 5: (16.0%) with a relative adduct level 1.6×10-7. Rechromatography analyses indicates that DNA adducts 1-3 formed in HL-60 cells treated with p-cresol and after myeloperoxidase activation of p-cresol were similar to those formed by reaction of DNA with PCQM. This observation suggests that p-cresol is activated to a quinone methide intermediate in each of these activation systems. Taken together, these results suggest PCQM is the reactive intermediate leading to the formation of DNA adducts in HL-60 cells treated with p-cresol. Furthermore, the DNA adducts formed by PCQM may provide a biomarker to assess occupational exposure to toluene.

KW - DNA adducts

KW - HL-60 cells

KW - Myeloperoxidase

KW - p-Cresol

KW - Toluene

UR - http://www.scopus.com/inward/record.url?scp=0037422462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037422462&partnerID=8YFLogxK

U2 - 10.1016/S0009-2797(02)00249-1

DO - 10.1016/S0009-2797(02)00249-1

M3 - Article

VL - 145

SP - 149

EP - 158

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

SN - 0009-2797

IS - 2

ER -