Reduced poly(ADP-ribosyl)ation in lymphocytes of laryngeal cancer patients: results of a case-control study.
Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme that is catalytically activated by DNA strand breaks, plays a complex role in DNA repair. Using NAD(+) as a precursor, it catalyzes the formation of ADP-ribose polymers, which are attached to various proteins. Defects in DNA repair pathways have been associated with increased risks for cancer in humans. We investigated whether differences in the activity of PARP are associated with the risk for laryngeal cancer. In a case-control study on genetic, lifestyle and occupational risk factors for laryngeal cancer, PARP activity was assessed as DNA damage-induced poly(ADP-ribose) formation in human peripheral blood lymphocytes by quantitative immunofluorescence analysis. Polymer formation was determined as the cellular response to bleomycin, a well-known inducer of DNA strand breaks, in lymphocytes from 69 laryngeal cancer patients and 125 healthy controls. The frequency of bleomycin-induced polymer formation, measured as mean pixel intensity, was significantly lower in cases (74.6, SE = 3.7) than in controls (94.5, SE = 3.5) and not influenced by smoking, age or sex. There was no significant difference between cases (59.1, SE = 5.2) and controls (50.5, SE = 3.7) in basal polymer formation (in cells not treated with bleomycin). When the highest tertile of polymer formation was used as the reference, the odds ratio for the lowest tertile of bleomycin-induced polymer formation was 3.79 (95% confidence interval 1.37-10.47, p = 0.01). Peripheral blood lymphocytes from laryngeal cancer patients thus showed significantly less bleomycin-induced poly(ADP-ribose) formation. Our results suggest that a reduced capacity of somatic cells to synthesize poly(ADP-ribose) might be associated with an increased risk for laryngeal cancer. The underlying mechanism remains to be investigated.
Rajaee-Behbahani
Nahid
N
Division of Toxicology and Cancer Risk Factors, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Schmezer
Peter
P
Ramroth
Heribert
H
Bürkle
Alexander
A
Bartsch
Helmut
H
Dietz
Andreas
A
Becher
Heiko
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D016022:Case-Control Studies; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D001761:Bleomycin; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases