| Co-Investigator(Kenkyū-buntansha) |
KANAMARU Tomoyo Nakamura Gakuen University, Faculty of Nutritional Sciences, Instructor, 栄養科学部, 助手 (50291836)
HARAGUCHI Koichi Daiichi College of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00258500)
AKITA Masaharu Kamakura Wemen's University, Assistant Processor, 家政学部, 講師 (30231822)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Non-dioxin-type PCBs such as CB118,CB138,CB153 and CB187 have been detected at high concentration in the liver, adipose tissues, blood and mother milk of mammals. In this study, the in vitro metabolisms of three 2,4,5-trichloro-substituted PCBs (CB118,CB138 and CB187) were studied using liver microsomes of rats, hamsters and guinea pigs. The guinea pig showed much higher activity to hydroxylate such PCBs than the rat and the hamster and formed two metabolites from CB118 (2-OH-CB126,2-OH-tetraCB), four metabolites from CB138(2'-OH-CB157,3'-OH-1-CB138, two OH-pentaCBs) and thee metabolites from CB187 (4'-OH-CB178,4'-OH-CB151,4-OH-CB187). Pretreatment of a famous cytochrome P450 (P450) inducer, phenobarbital, increased the activity in all species to 3〜5-fold of untreated animals. These results suggest that PB-inducible P450 enzymes such as rat CYP2B1, guinea pig CYP2B18 and hamster CYP2B play an important role in the metabolism of 2,4,5-trichloro-substituted PCBs. The major metabolite for
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med in the metabolism of CB118,CB138 and CB153 was a 2-OH metabolite which is formed via 2,3-epoxide intermediate. On the other hand in CB187 metabolism the 4- and 4'-OH metabolites were mainly formed, suggesting that CB187 metabolism proceeds via a 3,4-or 3,4'-epoxide and subsequent NIH-shift or dechlorination.
To develop the new methods to evaluate the toxicity of non-dioxin-type PCBs, we examined the effect of three PCBs,CB52,CB77 and CB118, on cultured rat embryos. Rat embryos on day 11.5 of gestation (plug day=0) were cultured for 48 hours. At 2 hr after the culture was started, CB52,CB77 and CB118 dissolved in DMSO were added to the medium at a concentration of 10 or 100 ppm. DMSO was added as a control vehicle. Heart rate of cultured rat embryos showed no change in all PCB-treated groups during 48 hr-culture. The exposure of 10 or 100 ppm of CB52 to rat embryos resulted in only slight kinky tail and edema. On the other hand, morphological abnormalities of maxilla, cleft lip and cacogenesis were observed in rat embryos exposed to 100 ppm of CB118. In CB77-treated groups, such morphological abnomalities was also obsenved at a concentration of 10 ppm. These results suggested that CB52,CB118 and CB77 showed the embryological toxicity dose-dependently with the order of CB77>CB118>CB52. Less
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