Intrinsic presence of poly (ADP-ribose) is significantly increased in malignant prostate compared to benign prostate cell lines.
Poly(ADP-ribosyl)ation plays important roles in cellular DNA repair mechanisms as well as in cellular proliferation and genomic stability. Four carcinoma cell lines, LNCaP, PC-3, C4-2 and MatLu, and one prostate epithelial cell line, PNT1A, were tested using the H10 antibody to poly(ADP-ribose) by Western blotting and FACS analysis for basal and activated (10 mM H2O2) PARP activity. In both analyses, higher levels of basal polymer were present in the LNCaP cell line than in the prostate epithelial cell line or the MatLu cell an line. LNCaP cells demonstrated greater than 90% positive analyzed cells in FACS analysis both before and after treatment with H2O2. PNT1A epithelial cells demonstrated evidence of polymer presence only after treatment with H2O2. Microsatellite instability due to increased oxidative damage in tumor cells has been proposed as a means for accumulation of genetic changes. As oxidative stress can stimulate poly(ADP-ribose) reactions, an increased presence of the polymer may indicate a high level of oxidative damage occurring in the tumor cells, contributing to higher levels of genetic instability towards progression.
McNealy
Tamara
T
Department of Urology, University Hospital, Theodor-Kutzer-Ufer, 68135 Mannheim, Germany.
Frey
Manfred
M
Trojan
Lutz
L
Knoll
Thomas
T
Alken
Peter
P
Michel
Maurice Stephan
MS
Trojon
Lutz
L
Knoll
Thanas
T
D000230:Adenocarcinoma / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D000328:Adult; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D004249:DNA Damage; D018450:Disease Progression; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D018384:Oxidative Stress; D011064:Poly Adenosine Diphosphate Ribose / Q000032:analysis*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology
D000903:Antibiotics, Antineoplastic; D009363:Neoplasm Proteins; D011064:Poly Adenosine Diphosphate Ribose; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases