Absence of stimulation of poly(ADP-ribose) polymerase activity in patients predisposed to colon cancer

L. Cristóvão, M. C. Lechner, P. Fidalgo, C. N. Leitão, F. C. Mira, J. Rueff

Research output: Contribution to journalArticle

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Abstract

Poly(ADP-ribose)polymerase (PARP) has been implicated in DNA repair mechanisms and the associated activity shown to markedly increase after DNA damage in carcinogen-treated cells. A defective DNA repair has been associated to the aetiology of human cancers. In order to assess the potential role of this enzyme in cellular response to DNA damage by γ-radiation, we studied the activity of PARP in patients with familial adenomatous polyposis (FAP). We compared poly(ADP-ribose)polymerase activity by the rate of incorporation of radioactivity from [ 3 H]adenine-NAD + into acid-insoluble material in permeabilized leucocytes from FAP patients and healthy volunteers. Concomitantly, the intracellular levels of NAD + - the substrate for the PARP - and the reduced counterpart NADH were determined using an enzymatic cycling assay 30 min after [ 60 Co] γ-ray cells irradiation. Our results demonstrate that a marked stimulation of PARP activity is produced upon radiation of the cells from healthy subjects but not in the FAP leucocytes, which concomitantly show a marked decrease in total NAD + /NADH content. Our observations point to a role of PARP in the repair of the γ-radiation-induced DNA lesions through a mechanism that is impaired in the cells from FAP patients genetically predisposed to colon cancer. The differences observed in PARP activation by γ-radiation in patients and healthy individuals could reflect the importance of PARP activity dependent on treatment with γ-rays. The absence of this response in FAP patients would seem to suggest a possible defect in the role of PARP in radiation-induced DNA repair in this cancer-prone disease.

Original languageEnglish
Pages (from-to)1628-1632
Number of pages5
JournalBritish Journal of Cancer
Volume77
Issue number10
DOIs
Publication statusPublished - 1 Jan 1998

Fingerprint

Poly(ADP-ribose) Polymerases
Colonic Neoplasms
Adenomatous Polyposis Coli
NAD
Radiation
DNA Repair
DNA Damage
Healthy Volunteers
Leukocytes
Enzyme Assays
Adenine
Carcinogens
Radioactivity
Neoplasms
Acids
DNA
Enzymes

Keywords

  • DNA repair
  • Familial adenomatous polyposis
  • Poly(ADP-ribose)polymerase
  • Radiation

Cite this

Cristóvão, L. ; Lechner, M. C. ; Fidalgo, P. ; Leitão, C. N. ; Mira, F. C. ; Rueff, J. / Absence of stimulation of poly(ADP-ribose) polymerase activity in patients predisposed to colon cancer. In: British Journal of Cancer. 1998 ; Vol. 77, No. 10. pp. 1628-1632.
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abstract = "Poly(ADP-ribose)polymerase (PARP) has been implicated in DNA repair mechanisms and the associated activity shown to markedly increase after DNA damage in carcinogen-treated cells. A defective DNA repair has been associated to the aetiology of human cancers. In order to assess the potential role of this enzyme in cellular response to DNA damage by γ-radiation, we studied the activity of PARP in patients with familial adenomatous polyposis (FAP). We compared poly(ADP-ribose)polymerase activity by the rate of incorporation of radioactivity from [ 3 H]adenine-NAD + into acid-insoluble material in permeabilized leucocytes from FAP patients and healthy volunteers. Concomitantly, the intracellular levels of NAD + - the substrate for the PARP - and the reduced counterpart NADH were determined using an enzymatic cycling assay 30 min after [ 60 Co] γ-ray cells irradiation. Our results demonstrate that a marked stimulation of PARP activity is produced upon radiation of the cells from healthy subjects but not in the FAP leucocytes, which concomitantly show a marked decrease in total NAD + /NADH content. Our observations point to a role of PARP in the repair of the γ-radiation-induced DNA lesions through a mechanism that is impaired in the cells from FAP patients genetically predisposed to colon cancer. The differences observed in PARP activation by γ-radiation in patients and healthy individuals could reflect the importance of PARP activity dependent on treatment with γ-rays. The absence of this response in FAP patients would seem to suggest a possible defect in the role of PARP in radiation-induced DNA repair in this cancer-prone disease.",
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Absence of stimulation of poly(ADP-ribose) polymerase activity in patients predisposed to colon cancer. / Cristóvão, L.; Lechner, M. C.; Fidalgo, P.; Leitão, C. N.; Mira, F. C.; Rueff, J.

In: British Journal of Cancer, Vol. 77, No. 10, 01.01.1998, p. 1628-1632.

Research output: Contribution to journalArticle

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AU - Lechner, M. C.

AU - Fidalgo, P.

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