Coffee consumption induces GSTP in plasma and protects lymphocytes against (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced DNA-damage: results of controlled human intervention trials.
A number of animal studies indicate that coffee protects against chemical induction of cancer; also human studies suggest that coffee consumption is inversely related with the incidence of different forms of cancer. The protective effects were attributed to induction of glutathione-S-transferases (GSTs) and aim of the present human study was to find out if coffee causes induction of GSTs and protects against DNA-damage caused by (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), the DNA-reactive metabolite of benzo(a)pyrene. Ten participants consumed 1L unfiltered coffee/d over 5 days. Before and after the intervention, saliva and blood were collected and the overall GST activity was measured with 1-chloro-2,4-dinitrobenzene (CDNB). Additionally, GSTP and GSTA were determined in plasma with immunoassays. In blood, only weak (p=0.042) induction of GST (CDNB) was found. Furthermore, pronounced (three-fold) induction of GSTP was observed in blood, whereas GSTA was not altered. No correlations were seen between induction of GST (CDNB) and GSTP activities and the GSTP1 genotypes of the participants. Also clinical parameters (creatinine, alanine, aminotransferase, aspartate aminotransferase, alkaline phosphatase), which are markers for organ damage, were monitored. None of them was altered by coffee, but serum cholesterol levels were slightly (not significantly) enhanced. In a second trial (n=7), GSTP induction by unfiltered and paper filtered coffees, differing in cafestol and kahweol contents, were compared. The participants consumed 1L coffee/d over 3 days. Again significant (three-fold) induction of GSTP was observed. The effects seen with the two coffees were identical, indicating that the diterpenoid concentrations are not responsible for the effects. In a further trial (n=7), the effect of coffee (unfiltered, 1L/d, 5 days) on BPDE induced DNA-migration was studied in comet assays. A 45% reduction effect was observed. Our findings show that coffee induces GSTP in humans and indicate that consumption may lead to protection towards polycyclic aromatic hydrocarbons.
Steinkellner
Hans
H
Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Hoelzl
Christine
C
Uhl
Maria
M
Cavin
Christophe
C
Haidinger
Gerald
G
Gsur
Andrea
A
Schmid
Rainer
R
Kundi
Michael
M
Bichler
Julia
J
Knasmüller
Siegfried
S
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000328:Adult; D000818:Animals; D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology*; D003069:Coffee / Q000737:chemistry / Q000378:metabolism*; D020552:Comet Assay; D004249:DNA Damage; D004032:Diet; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000097:blood*; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D010949:Plasma / Q000201:enzymology*; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism; D012463:Saliva / Q000201:enzymology
D016587:Antimutagenic Agents; D003069:Coffee; D007527:Isoenzymes; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D051549:Glutathione S-Transferase pi