Toxicological aspects of flavonoid interaction with biomacromolecules.
OBJECTIVE
Flavonoids are widely accepted as health promoting phytochemicals, however, some flavonoids show ability of direct interaction with DNA and/or enhance carcinogen activation into DNA modifying agents. Thus, their potential harmful effect on the human body should be examined in detail.


METHODS
Direct interaction of flavonoids (quercetin, rutin) with DNA was examined using square wave voltammetry on carbon paste electrode. Induction effect of selected flavonoids on content of cytochrome P450 1A1, carcinogens activating enzyme, in colon and liver microsomal samples of animals exposed to flavonoids was determined by Western blotting, using anti-cytochrome P450 1A1 specific antibody.


RESULTS
Of the natural flavonoids tested, induction of CYP1A1 was elicited by the typical citrus flavonoid naringenin in the colon, as well as by flavone in the liver. Moreover, synthetic beta-naphthoflavone and naturally occurring chrysin, quercetin and diosmin induced CYP1A1 in both tissues. The oxidation signals of guanine and adenine in the DNA molecule were decreased in the presence of flavonoids.


CONCLUSIONS
Although flavonoids are often considered to be safe because of their "plant origin", ingestion of flavonoids should be taken with caution. Enhanced expression of CYP1A1 in colon tissue might be responsible for increasing incidence of colorectal carcinoma in humans. Electrochemistry can be used to study the interactions of flavonoids and DNA.
Hodek
Petr
P
Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic. hodek@natur.cuni.cz
Hanustiak
Pavel
P
Krízková
Jitka
J
Mikelova
Radka
R
Krízková
Sona
S
Stiborová
Marie
M
Trnková
Libuse
L
Horna
Ales
A
Beklová
Miroslava
M
Kizek
René
R
D000225:Adenine / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004563:Electrochemistry; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity*; D019791:Guanidine / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D051381:Rats
D004277:DNA, Single-Stranded; D005419:Flavonoids; D019363:Cytochrome P-450 CYP1A1; D000225:Adenine; D019791:Guanidine