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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
Published on: December 19, 2019
Influence of Selenium-Binding Protein 1 on the Inhibitory Effect of Methionine in 1-Fluoro-2,4-dinitrobenzene-Induced
Takayuki Koga1, Makoto Hiromura1, Masayo Hirao-Suzuki2
1Department of Pharmaceutical Sciences, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
Abstract:
Allergic contact dermatitis (ACD) is a common skin disorder caused by contact with allergens. ACD treatment is based on patient education to avoid contact with allergens. However, sometimes patients may not be able to avoid the allergen because of its close proximity to their living environment. Thus, a novel therapeutic strategy that does not involve the avoidance of allergens is required. We previously reported that methionine, an essential amino acid, significantly suppressed ACD development caused by the repeated application of 1-fluoro-2,4-dinitrobenzene (DNFB). However, the magnitude of this suppressive effect of methionine depended on the mouse strain used to establish ACD, and the mechanism of this difference was still unclear in past studies. In this study, we investigated the mechanism underlying these strain differences and found that a lack of selenium-binding protein 1 (SBP1) enhanced the ACD-suppressive effect of methionine. The lack of SBP1 does not affect ACD progression; however, it reduces the hepatic beta-homocysteine methyltransferase (Bhmt) expression suppression by ACD. In support of this hypothesis, the lack of SBP1 reduced the suppression of hepatic dimethylglycine (DMG) production by ACD. These results suggest that the lack of SBP1 enhances the suppressive effects of methionine on ACD by suppressing DMG production.
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