Effect of dietary tannic acid on epidermal, lung, and forestomach polycyclic aromatic hydrocarbon metabolism and tumorigenicity in Sencar mice.
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.
Athar
M
M
Department of Dermatology, University Hospitals of Cleveland, Ohio.
Khan
W A
WA
Mukhtar
H
H
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*
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