Modulation by plant flavonoids and related phenolics of microsome catalyzed adduct formation between benzo[a]pyrene and DNA.
Twenty-six flavonoids and related compounds were screened for their ability to modulate microsome mediated covalent adduct formation between [3H]benzo[a]pyrene ([3H]BP) and DNA in vitro. Some of these flavonoids, notably robinetin, quercetin, isorhamnetin and kaempferol were observed to inhibit the adduct formation significantly at very low levels. The unsubstituted flavone and some of the other flavonoids moderately inhibited this adduct formation, while some flavonoids were inactive, viz., most of the isoflavonoids and methylether derivatives of polyhydroxylated flavonoids. Structural features contributory towards the inhibitory activity of flavonoids appeared to be hydroxyl groups in 3 position of C ring, 5,7-positions of A ring and 3',4'- and 5'-positions of B ring. Methylation or glycosylation of hydroxyl group rendered the flavonoid less active or inactive. Flavanones, with saturated 2,3 double bond, were also inactive. Metabolic activation of BP to proximate carcinogen (+/-)-trans-7,8-dihydroxy-7,8-dihydro-BP (BP-7,8-dihydrodiol) was also measured in presence of some of these flavonoids. The extent of inhibition of metabolism by these flavonoids did not correlate with their ability to inhibit the adduct formation. Thus, suppression of metabolism did not appear to be a major contributory factor towards inhibition of adduct formation. The solvolysis in aqueous dioxane of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydro-BP (BPDE I), the ultimate carcinogen of BP, was accelerated in presence of selected flavonoids. Inactivation of BPDE I, therefore, appeared to be the major mechanism by which some of these flavonoids inhibited the adduct formation between BP and DNA, and this could be the basis for the anti-carcinogenic nature of these flavonoids.
D001564:Benzo(a)pyrene / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism*; D066298:In Vitro Techniques; D008861:Microsomes / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D010944:Plants; D013329:Structure-Activity Relationship
D001580:Benzopyrenes; D004101:Dihydroxydihydrobenzopyrenes; D005419:Flavonoids; D010636:Phenols; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; D004247:DNA