Changes in the mutagenic and estrogenic activities of bisphenol A upon treatment with nitrite.
Bisphenol A (4,4'isopropylidenediphenol: BPA), an endocrine-disrupting chemical, is contained in food-packaging and can-coating agents as well as in dental sealants. Nitrite is present in vegetables, fish and tap water as an ingredient or contaminant, and also in human saliva. Here, we explored the possible generation of genotoxicity from the reactions of BPA and nitrite under acidic conditions, a situation simulating the stomach. We determined the changes in the mutagenic and estrogenic activities of BPA before and after nitrite treatment. Untreated BPA did not exhibit any mutagenicity. However, the mixture of BPA and sodium nitrite after incubation at pH 3.0 showed strong mutagenic activity toward Salmonella typhimurium strains TA 100 and TA 98 either with or without a metabolic activation system (S9 mix). The clastogenic properties of nitrite-treated and untreated BPA were analyzed by a micronucleus test with male ICR mice. A single gastric intubation of nitrite-treated BPA induced a significantly higher frequency of micronucleated reticulocytes (MNRETs) in mice. The results of analysis of electron spin resonance (ESR) suggest that the expression of the mutagenic activity of nitrite-treated BPA is related to the generation of radicals in the reaction mixture. By applying 1H and 13C NMR, AB-MS and APCI/LC/MS, we identified two compounds 3-nitrobisphenol A and 3,3'-dinitro-bisphenol A. These compounds were synthesized by the reaction of BPA with nitric acid. 3,3'-Dinitro-bisphenol induced a significantly greater frequency of MNRETs in male ICR mice. By applying a green fluorescent protein (GFP)-reporter expression system and an estrogen R(alpha) competitor screening kit, we found that nitrite-treated BPA and 3,3'-dinitro-bisphenol A showed weak estrogenic activity compared to that of untreated BPA.
Masuda
Shuichi
S
Graduate School of Nutritional and Environmental Sciences, COE Program in the 21st Century, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. masudas@smail.u-shizuoka-ken.ac.jp
Terashima
Yumeko
Y
Sano
Ayako
A
Kuruto
Ryoko
R
Sugiyama
Yasumasa
Y
Shimoi
Kayoko
K
Tanji
Kenichi
K
Yoshioka
Hisashi
H
Terao
Yoshiyasu
Y
Kinae
Naohide
N
D000818:Animals; D001559:Benzhydryl Compounds; D001667:Binding, Competitive; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D009573:Nitrites / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012156:Reticulocytes / Q000187:drug effects / Q000502:physiology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D016339:Spectrometry, Mass, Fast Atom Bombardment; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D049452:Green Fluorescent Proteins; D009153:Mutagens; D009573:Nitrites; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds