title: Butylated hydroxyanisole produces both mutagenic and desmutagenic derivatives under gastric conditions.
abstract: Dietary butylated hydroxyanisole (BHA) has been known to have inconsistent functions on carcinogenesis, both prevention and initiation. We assumed that both functions of BHA were introduced by the derivatives formed after the reaction with gastric components such as nitrite in the stomach. We then identified the derivatives produced by incubating BHA with sodium nitrite at pH 2.0 or pH 5.0. Eight derivatives were detected; 2-tert.-butyl-p-quinone (BQ), 3,3'-di-tert.-butyl-biphenyldiquinone-(2,5,2',5') (BBDQ), 2,6-di-tert.-butyl-8-hydroxy-dibenzofuran-1,4-quinone (BHDQ), 6-nitro-BHA, 2,2'-dihydroxy-3,3'-di-tert.-butyl-5,5'-dimethoxy-biphenyl (di-BHA), an oxidized product of di-BHA, and two unstable reaction intermediates. BQ was a major final product at pH 2.0, but not at pH 5.0. 6-Nitro-BHA and the oxidized products of di-BHA were also the final products. BBDQ was formed from di-BHA and easily converted to BHDQ. Their mutagenicity and desmutagenicity were assayed using Salmonella typhimurium strains. BQ and BBDQ were the mutagens of base-substitution type, BHDQ was the potent desmutagen against a mutagenicity of Trp-P-2, and the others had neither of the two activities. Thus, BHA was found to produce both the mutagen and desmutagen under the gastric conditions. BQ has been previously reported to be easily detoxified by glutathione, and BHA itself is well known to prevent carcinogenesis. In the assessment of dietary BHA on carcinogenesis, since one of the mutagens from BHA is easily detoxified in our bodies and another is converted to a desmutagen, BHA appears to be one of the favourable chemicals for us.
authors.affiliation: Department of Agricultural Chemistry, Kobe University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kanazawa
authors.forename: M
authors.initials: M
authors.lastname: Mizuno
mesh_terms: D016588:Anticarcinogenic Agents / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000378:metabolism*; D002243:Carbolines / Q000037:antagonists & inhibitors*; D005750:Gastric Juice / Q000378:metabolism*; D015394:Molecular Structure; D009153:Mutagens / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000378:metabolism; D012977:Sodium Nitrite / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D002243:Carbolines; D009153:Mutagens; D002083:Butylated Hydroxyanisole; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D012977:Sodium Nitrite