Biochemical and enzymatic aspects of caffeine and caffeine derivatives induced DNA strand breaks.
The results presented here point to the difficulties that exist in connection with the identification of the molecular target of caffeine. Our data support the evidence that caffeine and caffeine derivatives cause DNA-protein cross-links (DPC) in whole mammalian cells or in isolated nuclei. These DPC have the same properties (saturability, reversibility and temperature-dependence) as those produced by an enzymatic inhibition. The experiments performed in reconstituted systems, in the presence of purified DNA topoisomerase II, do not support the original hypothesis that this enzyme might be a possible target for this class of drugs. We suggest the possibility that other DNA metabolism enzymes are involved in the biological effects of caffeine and caffeine derivatives. Further biochemical and molecular data are necessary to identify which of these enzymes is in fact affected.
Russo
P
P
Zignaigo
G
G
Lusuriello
P
P
Tornaletti
S
S
Pedrini
A M
AM
Parodi
S
S
D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives / Q000633:toxicity*; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000187:drug effects*; D006801:Humans; D007939:Leukemia L1210 / Q000201:enzymology / Q000235:genetics
D004277:DNA, Single-Stranded; D002110:Caffeine; D004250:DNA Topoisomerases, Type II