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൳ೞ༗ᅊыѓ Caco-2 ੍ၘџохѿ P- ұӥӃҡ૱࠘ᄭѢ ᄐџࡸѰэӋӥҰ [e] ӆӞӥќӋӥҰ [a] ӆӞӥѢ۬ࢽ̡
ཾી५
ౄ९ྗ̝আઆࡶྗથ̝ܱႏ൦ბ̝ჸᇱბ̝ྑᇭྗ̝ॾჿৗ໐
Toxicology in Vitro, 21, 827-834 (2007)
Effects of benzo(e)pyrene and benzo(a)pyrene on P-glycoprotein-mediated transport in Caco-2 cell monolayer: a comparative approach
Narumi Sugihara, Kumiko Toyama, Tastuaki Okamoto, Masaaki Kadowaki, Kazumi Terao and Koji Furuno
ABSTRACT: The previous studies from our laboratory reported that benzo(a)pyrene (Bap) inß uenced efß ux transport of rhodamine 123 (Rho-123) by induction of P-glycoprotein (P-gp) in Caco-2 cells. The present study investigated whether induction of P-gp and the enhanced efflux transport of Rho-123 were caused by benzo(e)pyrene (Bep), which has a structure similar to Bap, but is not a carcinogenic compound. In Caco-2 monolayer exposed to 50
?M Bep for 72 hrs, the ratio of the apparent permeability coefÞ cient (Papp) of Rho-123 efß ux increased signiÞ cantly compared to that of the control monolayer. Similarly, a signiÞ cant increase in expression of MDR1 mRNA and of P-gp at the protein level were detected by RT- PCR and by Western blot analysis, respectively, in Caco-2 cells exposed to Bep, compared to that of the control. Caco-2 cells exposed to Bep showed oxidative stress that was detected by ß uorescence microscopy using aminophenyl ß uorescein. However, the oxidative stress was weaker compared with that of Bap. The cellular GSH content was decreased to 80 % or 59 % of control cells, respectively, in Caco-2 cells exposed to either Bep or Bap. Our results further show that Bep or Bap-induced P-gp in Caco-2 cells might have been the result of oxidative stress rather than DNA damage.
ᇩ̛य़ࢅ૭ќѤшҁѳќѠ̝ӌӦұ[a]ӇӟӦ(Bap)҇ၰᇕьєCaco-2ၙѠпй ћ̝P-ҲӦӄҢсॶᄥຐъҁRhodamine-123(Rho-123)ѣၙޓѭѣ༎ୟсۭࢾ
҇ଦцҀшѝ҇၈ਇьћйҀ̞ਘݸѣय़ࢅќѤ̝BapѝഉѣᆭౖѤзҀс̝с
҈ᅀѣџйӌӦұ[e]ӇӟӦ(Bep)ѠпцҀ̝Rho-123ѣၙޓ༎ୟѣഊకᅀѠљ йћѮє̞
̜Bep50ȝM҇ 83 ࠗၰᇕъѐє൴༘ᅋѣCaco-2ၙѠпйћ̝Rho-123ѣ༎ୟၒ ষѣPappѤҦӦһӠ̷Ӟ༘ᅋ൴ၙѠཿѮћᄜڞѠഄ݈ьє̞ຎѠ̝MDR1ѣ mRNAѣॶѹҲӦӄҢӟӌӞќѣP-ҲӦӄҢѣഄൌс̝RT-PCRѹWestern
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blotݷ౸Ѡѽѿग़ୟъҁє̞BepѠၰᇕъѐєCaco-2ၙѤ̝aminophenyl fluorescein
҇ᅀйєऱর५ྒࢽࠒੴѠѽѿઓ݂ษҬһӟҬсޱъҁє̞ьрь̝ђѣઓ݂ษҬ һӟҬѤBapѠཿѮћଖрјє̞ၙѣGSHᆙѤ̝BepзҀйѤBapѠၰᇕъѐє
ၙѠпйћ̝ђҁѓҁҦӦһӠ̷Ӟၙѣ 91ͮзҀйѤ 6:ͮѠॳஜьћйє̞шҁ ѾѣॆݑрѾ̝Caco-2ၙѠпцҀBepзҀйѤBapၰᇕѠѽҀP-ҲӦӄҢѣᄥ
ຐѤ̝DNAഠќѤџф̝ઓ݂ษҬһӟҬс࠙ᄮьћйҀౖ݉сਫъҁє̞
