Flavonoids inhibit genetic toxicity produced by carcinogens in cells expressing CYP1A2 and CYP1A1.
The effects of the flavonoids quercetin, apigenin and chrysin (10 microM) on the genetic toxicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and benzo[a]pyrene (BaP) was investigated at sub-cytotoxic concentrations in Chinese hamster V79 cells expressing human or rat cytochromes P450. In V79 r1A2-NH and V79 h1A1-MZ cells, none of the flavonoids increased DNA strand breaks (SB) (measured by the Comet assay) or produced detectable DNA adducts (measured by 32P-post-labelling). Neither IQ nor BaP produced DNA damage in the absence of expressed CYP1A2 or CYP1A1, respectively. DNA damage measured as SB and DNA adducts was detectable in V79 r1A2-NH cells expressing rat CYP1A2 when treated with IQ (2.5-50 microM) and this was inhibited by quercetin. Likewise, DNA damage (SB and DNA adducts) was elevated in V79 h1A1-MZ cells expressing human CYP1A1 when treated with BaP (0.1-0.5 microM) and this was inhibited by chrysin and apigenin, but not by quercetin. The specificity of CYP1A1 inhibition by chrysin and apigenin and CYP1A2 inhibition by quercetin was confirmed by ethylresorufin O-deethylase assay.
Lautraite
S
S
School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
Musonda
A C
AC
Doehmer
J
J
Edwards
G O
GO
Chipman
J K
JK
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D047310:Apigenin; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001711:Biotransformation / Q000187:drug effects; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002478:Cells, Cultured / Q000187:drug effects; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000502:physiology*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D018736:DNA Adducts / Q000032:analysis; D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008168:Lung; D008297:Male; D009152:Mutagenicity Tests; D011355:Prodrugs / Q000378:metabolism / Q000633:toxicity*; D011794:Quercetin / Q000494:pharmacology*; D011804:Quinolines / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D013045:Species Specificity
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D018736:DNA Adducts; C096278:DNA-(2-amino-3-methylimidazo(4,5-f)quinoline) adduct; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011355:Prodrugs; D011804:Quinolines; D011993:Recombinant Fusion Proteins; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; C043561:chrysin; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D047310:Apigenin; D011794:Quercetin; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline