Reference

The in vivo exposure to plant flavonols

The in vivo exposure to plant flavonols. Influence on frequencies of micronuclei in mouse erythrocytes and sister-chromatid exchange in rabbit lymphocytes. MacGregor, James T.; Wehr, Carol M.Several substances are used for example 117-39-5 which is its cas registry number.; Manners, Gary D.; Jurd, Leonard; Minkler, Jason L.; Carrano, Anthony V. (Western Reg. Res. Cent., U.S. Dep. Agric., Berkeley, CA 94710, USA). Mutat. Res., 124(3-4), 255-70 (English) 1983. CODEN: MUREAV. ISSN: 0027-5107. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) No consistent increases in the micronucleus frequency were obsd. in bone marrow or peripheral blood erythrocytes from mice treated with quercetin (I) [117-39-5], rhamnetin [90-19-7],neohesperidin dihydrochalcone [20702-77-6], or hesperetin dihydrochalcone [35400-60-3] under various exposure and sampling conditions. Over the dose range of 100-1000 mg/kg, I failed to increase significantly erythrocyte micronucleus frequencies either in bone marrow of male mice at 6 h after the 2nd of 2 i.p. or oral doses given 24 h apart, or at 48, 96, or 192 h after a single i.p. or oral dose, or in peripheral blood of male or female mice sampled for 7 consecutive days following a single i.p. dose. Feeding 5 or 10% I for 8 days also failed to increase the micronucleus frequency in bone marrow erythrocytes of female or male mice. Hesperetin dihydrochalcone and neohesperidin dihydrochalcone, at oral doses of 100-1000 mg/kg, did not increase the micronucleus frequency in bone marrow erythrocytes 6 h after the 2nd doses 24 h apart, nor did rhamnetin at 48 or 96 h after a single i.p. dose of 100 mg/kg. Galangin [548-83-4], in contrast, did increase the micronucleus frequency in bone marrow and blood erythrocytes under certain conditions, but the largest increases were only 2-3-times control values and these were obsd. at highly toxic doses. Rabbits given up to 250 mg/kg I i.p. showed no treatment-related increase in the sister chromatid-exchange frequency in peripheral blood lymphocytes sampled at 1 and 7 days after treatment. These results fail to confirm published data which report a markedly increased frequency of micronuclei in bone marrow erythrocytes from I-treated mice, show no I-related alterations in the sister chromatid-exchange frequency in rabbit lymphocytes, and indicate that clastogenesis in bone marrow erythoblasts due to oral or i.p. administration of the flavonols studied is at most very weak. .

Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by phenolic plant flavonoids

Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by phenolic plant flavonoids. Huang, Mou Tuan; Wood, Alexander W.; Newmark, Harold L.; Sayer, Jane M.; Yagi, Haruhiko; Jerina, Donald M.; Conney, Allan H. (Dep. Biochem. Drug Metab., Hoffmann-La Roche Inc., Nutley, NJ 07110, USA). Carcinogenesis (London), 4(12), 1631-7 (English) 1983. CODEN: CRNGDP. ISSN: 0143-3334. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Myricetin [529-44-2], robinetin [490-31-3], and luteolin [491-70-3] inhibited the mutagenic activity resulting from the metabolic activation of benzo[a]pyrene (I) [50-32-8] and (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene [61443-57-0] by rat liver microsomes. These naturally occurring plant flavonoids and 17 addnl. flavonoids and related derivs. with phenolic hydroxyl groups inhibited the mutagenic activity of (±)-7b,8a-dihydroxy-9a,10a-epoxy-7,8,9,10-tetrahydrobenzo[a]pyren e (B[a]P 7,8-diol-9,10-epoxide-2) [58917-67-2], which is an ultimate mutagenic and carcinogenic metabolite of I. Several flavonoids without phenolic hydroxyl groups of methylated phenolic hydroxyl groups were inactive. The mutagenic activity of 0.05 nmol BP 7,8-diol-9,10-epoxide-2 towards strain TA 100 of Salmonella typhimurium was inhibited 50% by incubation of the bacteria and the diol-epoxide with myricetin (2nmol), luteolin (5 nmol), quercetin [117-39-5] (5 nmol), 7-methoxyquercetin [90-19-7] (5 nmol), rutin [153-18-4] (5 nmol), quercitrin [522-12-3] (5 nmol), delphinidin chloride [528-53-0] (5 nmol), morin [480-16-0] (10 nmol), myricitrin [17912-87-7] (10 nmol), kaempferol [520-18-3] (10 nmol), diosmetin [520-34-3] (10 nmol), fisetin [528-48-3] (10 nmol), or apigenin [520-36-5] (10 nmol). Considerably less antimutagenic activity was obsd. for dihydroquercetin [480-18-2], naringenin [480-41-1], robinin [301-19-9], D-catechin [154-23-4], genistein [446-72-0], kaempferide [491-54-3], and chrysin [480-40-0]. Pentamethoxyquercetin [1247-97-8], tangeretin [481-53-8], nobiletin [478-01-3], 7,8-benzoflavone [604-59-1], 5,6-benzoflavone [6051-87-2], and flavone [525-82-6], which lack free phenolic groups, were inactive. The antimutagenic activity of hydroxylated flavonoids results from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2 since the rate of disappearance of the diol-epoxide from cell-free solns. in 1:9 dioxane:water was markedly stimulated by myricetin, robinetin, and quercetin. Myricetin was a highly potent inhibitor of the mutagenic activity of bay-region diol-epoxides of I, dibenzo[a,h]pyrene and dibenzo[a,i]pyrene, but higher concns. of myricetin were needed to inhibit the mutagenicity of the chem. less reactive benzo[a]pyrene 4,5-oxide and bay region diol-epoxides of benz[a]anthracene, chrysene, and benzo[c]phenanthrene.