Induction of poly(ADP-ribosyl)ation and DNA damage in human peripheral lymphocytes after treatment with (-)-epigallocatechin-gallate.
With regard to a future use of tea polyphenols in intervention trials with individuals at high cancer risk, the effects of the tea ingredient (-)-epigallocatechin gallate (EGCG) on poly(ADP-ribose) (PAR) levels and on DNA damage were investigated in human lymphocytes. A dose- and time-dependent elevation of both PAR formation as assessed by quantitative immunofluorescence analysis and DNA damage as assessed by the comet assay were observed after treatment with EGCG at 20, 40 and 80 microM for 10-240 min. Maximum levels of PAR formation and of DNA damage were observed after 10 min at all concentrations tested. Increased PAR levels were still detectable by 240 min in the 40 and 80 microM groups. At the lowest concentration, which is near the physiological peak values found after tea ingestion, PAR formation was not correlated with DNA damage. Here, EGCG led to pronounced PAR levels, whereas the comet assay was almost negative. In contrast, such marked differences in time course and extent of both genotoxicity and PAR formation following EGCG treatment were not detected after gamma-irradiation. Our results suggest that the known chemopreventive effects of EGCG, the main constituent of tea, may be partly attributed to an induction of PAR formation.
Bertram
Barbara
B
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany. b.bertram@dkfz.de
Bollow
Ursula
U
Rajaee-Behbahani
Nahid
N
Bürkle
Alexander
A
Schmezer
Peter
P
D016587:Antimutagenic Agents / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D018675:Toxicity Tests
D016587:Antimutagenic Agents; D011064:Poly Adenosine Diphosphate Ribose; D002392:Catechin; C045651:epigallocatechin gallate