title: Effect of dietary tannic acid on epidermal, lung, and forestomach polycyclic aromatic hydrocarbon metabolism and tumorigenicity in Sencar mice.
abstract: Tannic acid inhibits the mutagenicity of several polycyclic aromatic hydrocarbons (PAHs) and their bay-region diol-epoxides. Our prior studies have shown that when applied topically to Sencar mice, tannic acid caused substantial inhibition of epidermal PAH metabolism, subsequent PAH-DNA adduct formation, and PAH-induced skin tumorigenesis (H. Mukhtar et al., Cancer Res., 48:2361-2365, 1988, and references therein). In this study the effects of tannic acid supplementation in the diet (1%, w/w, in AIN-76 diet) of Sencar mice on benzo(a)pyrene (BP) metabolism and its subsequent DNA binding and tumorigenesis in lung and forestomach were evaluated. Animals receiving a tannic acid-containing diet showed diminished aryl hydrocarbon hydroxylase and 7-ethoxy-resorufin O-deethylase activities in the forestomach and lung. Elevated glutathione S-transferase and NAD(P)H:quinone reductase activities were observed in these tissues. Maximum effects occurred after 45 days of feeding. Administration of [3H]BP p.o. to animals resulted in lower covalent binding to DNA in forestomach and lung of animals receiving tannic acid-containing diet as compared to animals receiving AIN-76 control diet. Tumor induction studies in forestomach and lung revealed significant protection against BP-induced tumorigenesis in animals fed tannic acid-supplemented diet as compared to animals fed control diet. The mice fed tannic acid-supplemented diet developed 3.3 forestomach tumors/mouse compared to 5.2 tumors/mouse in animals receiving control diet. The numbers of pulmonary tumors per mouse in animals fed tannic acid-supplemented diet and control diet were 1.6 and 3.1, respectively. Topical application of 7,12-dimethylbenz(a)anthracene to animals fed tannic acid-supplemented diet did not result in significant protection against skin tumorigenesis. However, a slight delay in the onset of skin tumor formation occurred in tannic acid-fed animals when compared to animals receiving control diet. Our data suggest that dietary supplementation with tannic acid affords protection against BP-induced forestomach and lung tumorigenesis in rodents.
authors.affiliation: Department of Dermatology, University Hospitals of Cleveland, Ohio.
authors.forename: M
authors.initials: M
authors.lastname: Athar
authors.forename: W A
authors.initials: WA
authors.lastname: Khan
authors.forename: H
authors.initials: H
authors.lastname: Mukhtar
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000302:isolation & purification / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000302:isolation & purification; D018736:DNA Adducts; D004032:Diet; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008175:Lung Neoplasms / Q000139:chemically induced*; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013270:Stomach / Q000187:drug effects; D013274:Stomach Neoplasms / Q000139:chemically induced*; D013634:Tannins / Q000494:pharmacology*
chemical_list: D018736:DNA Adducts; D047348:Hydrolyzable Tannins; D013634:Tannins; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases