Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells

Hua Fung, Yoke W. Kow, Bennett Van Houten, Douglas J. Taatjes, Zafer Hatahet, Yvonne M.W. Janssen, Pam Vacek, Stephen P. Faux, Brooke T. Mossman

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Only two DNA repair enzymes, DNA polymecase β and O6-methylguanine- DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothetioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 μg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.

Original languageEnglish (US)
Pages (from-to)189-194
Number of pages6
JournalCancer Research
Volume58
Issue number2
StatePublished - Jan 15 1998

Fingerprint

Endonucleases
Asbestos
DNA Repair Enzymes
Gene Expression
Enzymes
Proteins
Crocidolite Asbestos
DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA
Methyltransferases
Oxidants
Confocal Microscopy
Carcinogens
Glass
Mitochondria
Stem Cells
Lung
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Fung, H., Kow, Y. W., Van Houten, B., Taatjes, D. J., Hatahet, Z., Janssen, Y. M. W., ... Mossman, B. T. (1998). Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. Cancer Research, 58(2), 189-194.
Fung, Hua ; Kow, Yoke W. ; Van Houten, Bennett ; Taatjes, Douglas J. ; Hatahet, Zafer ; Janssen, Yvonne M.W. ; Vacek, Pam ; Faux, Stephen P. ; Mossman, Brooke T. / Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. In: Cancer Research. 1998 ; Vol. 58, No. 2. pp. 189-194.
@article{8cf21594fd8b4011ab89596fbdc582c3,
title = "Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells",
abstract = "Only two DNA repair enzymes, DNA polymecase β and O6-methylguanine- DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothetioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 μg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.",
author = "Hua Fung and Kow, {Yoke W.} and {Van Houten}, Bennett and Taatjes, {Douglas J.} and Zafer Hatahet and Janssen, {Yvonne M.W.} and Pam Vacek and Faux, {Stephen P.} and Mossman, {Brooke T.}",
year = "1998",
month = "1",
day = "15",
language = "English (US)",
volume = "58",
pages = "189--194",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

Fung, H, Kow, YW, Van Houten, B, Taatjes, DJ, Hatahet, Z, Janssen, YMW, Vacek, P, Faux, SP & Mossman, BT 1998, 'Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells', Cancer Research, vol. 58, no. 2, pp. 189-194.

Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. / Fung, Hua; Kow, Yoke W.; Van Houten, Bennett; Taatjes, Douglas J.; Hatahet, Zafer; Janssen, Yvonne M.W.; Vacek, Pam; Faux, Stephen P.; Mossman, Brooke T.

In: Cancer Research, Vol. 58, No. 2, 15.01.1998, p. 189-194.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells

AU - Fung, Hua

AU - Kow, Yoke W.

AU - Van Houten, Bennett

AU - Taatjes, Douglas J.

AU - Hatahet, Zafer

AU - Janssen, Yvonne M.W.

AU - Vacek, Pam

AU - Faux, Stephen P.

AU - Mossman, Brooke T.

PY - 1998/1/15

Y1 - 1998/1/15

N2 - Only two DNA repair enzymes, DNA polymecase β and O6-methylguanine- DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothetioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 μg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.

AB - Only two DNA repair enzymes, DNA polymecase β and O6-methylguanine- DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothetioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 μg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.

UR - http://www.scopus.com/inward/record.url?scp=0031984582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031984582&partnerID=8YFLogxK

M3 - Article

C2 - 9443389

AN - SCOPUS:0031984582

VL - 58

SP - 189

EP - 194

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 2

ER -