DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine

Mary Jo Dorie, Mary S. Kovacs, Edward C. Gabalski, Markus Adam, Quynh T. Le, Daniel A. Bloch, Harlan A. Pinto, David J Terris, J. Martin Brown

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone™] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

Original languageEnglish (US)
Pages (from-to)461-467
Number of pages7
JournalNeoplasia
Volume1
Issue number5
StatePublished - Nov 1 1999
Externally publishedYes

Fingerprint

tirapazamine
Comet Assay
Head and Neck Neoplasms
DNA Damage
Neoplasms
Oxygen

Keywords

  • Comet assay
  • Eppendorf
  • Hypoxia
  • Radiotherapy
  • Tirapazamine

ASJC Scopus subject areas

  • Cancer Research

Cite this

Dorie, M. J., Kovacs, M. S., Gabalski, E. C., Adam, M., Le, Q. T., Bloch, D. A., ... Brown, J. M. (1999). DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine. Neoplasia, 1(5), 461-467.

DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine. / Dorie, Mary Jo; Kovacs, Mary S.; Gabalski, Edward C.; Adam, Markus; Le, Quynh T.; Bloch, Daniel A.; Pinto, Harlan A.; Terris, David J; Brown, J. Martin.

In: Neoplasia, Vol. 1, No. 5, 01.11.1999, p. 461-467.

Research output: Contribution to journalArticle

Dorie, MJ, Kovacs, MS, Gabalski, EC, Adam, M, Le, QT, Bloch, DA, Pinto, HA, Terris, DJ & Brown, JM 1999, 'DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine', Neoplasia, vol. 1, no. 5, pp. 461-467.
Dorie MJ, Kovacs MS, Gabalski EC, Adam M, Le QT, Bloch DA et al. DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine. Neoplasia. 1999 Nov 1;1(5):461-467.
Dorie, Mary Jo ; Kovacs, Mary S. ; Gabalski, Edward C. ; Adam, Markus ; Le, Quynh T. ; Bloch, Daniel A. ; Pinto, Harlan A. ; Terris, David J ; Brown, J. Martin. / DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine. In: Neoplasia. 1999 ; Vol. 1, No. 5. pp. 461-467.
@article{b37f9d432eda4d11bef5cbaf8a95ee3a,
title = "DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine",
abstract = "Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone™] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.",
keywords = "Comet assay, Eppendorf, Hypoxia, Radiotherapy, Tirapazamine",
author = "Dorie, {Mary Jo} and Kovacs, {Mary S.} and Gabalski, {Edward C.} and Markus Adam and Le, {Quynh T.} and Bloch, {Daniel A.} and Pinto, {Harlan A.} and Terris, {David J} and Brown, {J. Martin}",
year = "1999",
month = "11",
day = "1",
language = "English (US)",
volume = "1",
pages = "461--467",
journal = "Neoplasia (United States)",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine

AU - Dorie, Mary Jo

AU - Kovacs, Mary S.

AU - Gabalski, Edward C.

AU - Adam, Markus

AU - Le, Quynh T.

AU - Bloch, Daniel A.

AU - Pinto, Harlan A.

AU - Terris, David J

AU - Brown, J. Martin

PY - 1999/11/1

Y1 - 1999/11/1

N2 - Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone™] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

AB - Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone™] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

KW - Comet assay

KW - Eppendorf

KW - Hypoxia

KW - Radiotherapy

KW - Tirapazamine

UR - http://www.scopus.com/inward/record.url?scp=0033222410&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033222410&partnerID=8YFLogxK

M3 - Article

C2 - 10933062

AN - SCOPUS:0033222410

VL - 1

SP - 461

EP - 467

JO - Neoplasia (United States)

JF - Neoplasia (United States)

SN - 1522-8002

IS - 5

ER -