3456 Superinduction of cytochrome P450 1A1 by bisphenol-A derivatives
S. HIKAGE1, T. SAITO2, Y. TAKAHASHI2, T. KAMATAKI2, T. HONGO3, and K. SAKAGUCHI1, 1Health Sciences University of Hokkaido, Tobetsu-Cho, Japan, 2Hokkaido University, Sapporo, Japan, 3Tokyo Medical & Dental University, Japan

Objectives: We showed that bisphenol-A glycidyl methacrylate (Bis-GMA) resin monomer does induce cytochrome P450 (CYP) 1A1 in a previous report (IADR 79th general session, abstract #1330). The purpose of this study was to investigate the effects of bisphenol-A (BPA) and its derivatives (Bis-GMA and bisphenol-A diglycidyl ether (BADGE)) on the aromatic hydrocarbon-induced CYP1A1 expression. Methods: HepG2 cells were transfected with the human CYP1A1 promoter-luciferase chimeric gene using a calcium phosphate coprecipitation method. The cells were then exposed to the BPA derivatives and/or 1µM 3-methylcholanthrene (MC), and cultured at 37°C for 40 hours. After cultivation, the luciferase was extracted by cell lysis, and luciferase activity was determined with a luminometer. Luciferase activity was shown relative to the positive control (MC). The data were statistically analyzed by Student's t-test. Results: The relative luciferase activity with BPA, Bis-GMA or BADGE alone was 0.24±0.16, 0.34±0.38 or 0.05±0.03 at 50µM, while the relative luciferase activity in the presence of MC was 6.14±2.13, 10.21±4.63 or 3.84±0.89, respectively. The relative luciferase activity with BPA, Bis-GMA or BADGE in the presence of MC was significantly different from that with BPA, Bis-GMA or BADGE alone as well as from that of MC (p<0.05). In addition, Northern blot analysis indicated that BPA and its derivatives also enhanced the MC-induced expression of CYP1A1mRNA. Conclusions: These results suggest that BPA and its derivatives together with MC superinduce the human CYP1A1 gene.

Seq #315 - Biological Properties, Properties of Implants
11:00 AM-12:15 PM, Saturday, 9 March 2002 San Diego Convention Center Exhibit Hall C

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