• Archives of Pharmacal Research
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• 제16권4호
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• pp.276-282
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• 1993

This study has been undertaken to examine the effect of 3-methylcholanthrene (3MC) on rat uterine growth and to understand the mechanism of action of 3MC in rat uterus. After diethylstilbesterol(DES) or tamoxifen(TAM) or 3MC or DES plus TAM or DES plus 3MC was administered into immature female rats, uterine weight over corn oil-treated uteri. 3MC treatment had no effect on uterine weight but, DES stimulated uterine weight was inhibited by 3MC concomitant tratment. While TAM alone treatment showed slight increase in uterine wieght, inhibited uterine growth simulated by DES when it was adiministrated with DES condirect binding assay with $[^3H]$ estradiol and the relative binding affinities of 3MC and TAM were estimated by competetion assy. Estradiol tumed out to have high affinity for rat uterine estrogen receptor (kd = 0.4 nM). The relative binding affinities of TAM and 3MC were 1% and 4.7% that of DES for rat uterine estrogen receptor, respectively. 3MC was shown to have similar affinity for eat uterine estrogen receptor to that of TAM. Effects of DES 3MC and TAM administration in vivo on rat uterine estrogen recptor level were examined. It was confirmed that the estrogen, DES and antiestrogen, TAM decreased estrogen receptor levels from rat ulterus and also 3MC decreased rat uterine estrogen receptor level when rats were treated with DES, TAM and 3MC in vivo. Data indicates that 3MC acts as an antiestrogen mediated through estrogen receptor system.

• Applied Biological Chemistry
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• 제39권1호
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• pp.77-83
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• 1996

이스라엘 잉어에 있어서 carbamate계 살충제 carbofuran의 독성에 미치는 phenobarbital sodium(PB) 또는 3-methylcholanthrene (3-MC)의 영향과 작용기작을 효소적 측면에서 구명할 목적으로 carbofuran과 PB나 3-MC를 이스라엘 잉어에 각 조합으로 처리하여 독성경감 효과를 조사하였고, 공시한 농약과 PB나 MC가 acetylcholinesterase(AChE), glutathione S-transferase(GST), UDP-glucuronosyltransferase(UDPGT) 및 cytochrome P-450-dependent monooxygenase(monooxygenase)의 효소활성에 미치는 영향을 조사하기 위하여 carbofuran과 PB나 3-MC를 각각 조합으로 처리한 후 경시적으로 이스라엘 잉어의 각 효소들의 상대활성도를 조사하였다. PB와 3-MC만 투여한 실험군에서 이스라엘 잉어의 생존수는 무처리군과 동일하였고 살충제만 처리한 실험군의 이스라엘 잉어 생존수는 처리농도가 증가하면서 감소되었으나, PB나 3-MC와 살충제를 조합처리한 실험군에서는 살충제만 처리한 실힘군에 비하여 매우 높은 생존율을 나타낸 것으로 보아 해독효과가 인정 되었다. 효소활성(in vivo)은 AChE의 경우 carbofuran 0.95 ppm만을 처리한 실험군에서는 24시간내내 각 조사시기마다 무처리군에 비해 40% 이상의 활성저해를 보였으나 carbofuran과 PB 및 3-MC를 조합처리한 실험군에서는 효소활성이 초기에 감소하다가 서서히 증가하여 24시간후에는 무처리군과 비슷한 수준을 나타냈고, GST의 경우 carbofuran만을 처리한 실험군에서는 초기에 약 20% 이상의 활성저해를 보였으나 carbofuran과 PB나 3-MC를 조합처리한 실험군에서는 약제처리 1시간 후 부터 무처리군에 비해 효소활성이 20% 이상 증가하였다. UDPGT와 monooxygenase의 효소활성은 carbofuran과 PB나 3-MC를 조합처리한 실험에서 처리 $6{\sim}12$시간 후에는 carbofuran 처리군에 비해 효소활성이 $4{\sim}8$배 이상 급격히 높아졌다. 이상의 결과에서 PB 및 3-MC처리가 이들 효소의 활성을 유도함으로써 carbofuran의 독성으로 부터 이스라엘 잉어를 보호 하는데 관여한 것으로 보인다.

• 한국환경농학회지
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• 제21권1호
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• pp.57-68
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• 2002

쥐에서 carbofuran 대사에 미치는 phenobarbital sodium (PB) 또는 3-methylcholanthrene (3-MC)의 영향을 조사하기 위하여 쥐에 이들을 단독 또는 조합으로 경구투여한 후 일정 간격으로 쥐의 주요 장기, 대변, 소변 및 혈액 중 대사산물의 종류와 생성율을 조사하였다. Carbofuran 단독투여와 carbofuran과 PB 또는 3-MC 조합투여 모두 경구투여 후 48시간 이내에 빠르게 배설되어 $^{14}C$-carbofuran 총 투여량의 79.9$\sim$81.1%가 소변으로, 5.7$\sim$6.5%가 대변으로 배설되었는데, 배설속도는 carbofuran 단독투여 보다 carbofuran과 PB 또는 3-MC 조합투여에서 빨랐다. 쥐의 주요 장기, 대소변 및 혈액 중의 carbofuran의 대사산물은 공통적으로 3-hydroxycarbofuran, 3-ketorarbofuran, 3-hydroxycarbofuran phenol, 3-ketocarbofuran phenol과 carbofuran phenol이었고, 주요 대사산물은 3-hydroxycarbofuran과 3-ketocarbofuran이었는데, 주요 대사산물의 경우 carbofuran만의 투여에서는 3-hydroxycarbofuran이었으나 carbofuran과 PB 또는 3-MC 조합투여는 3-ketocarbofuran이었다. 소변 중 carbofuran의 2가지 주 대사산물의 생성율은 carbofuran 단독투여시 3-hydroxycarbofuran 17.4%와 3-ketocarbofuran 12.8%이었고, carbofuran과 PB 또는 3-MC 조합투여시 3-hydroxycarbofuran 8.6%와 3-ketocarbofuran 23.5%로서, carbofuran 단독투여와 carbofuran과 PB 또는 3-MC 투여사이에 대사산물의 종류는 같았으나 생성율에는 큰 차이가 있었다. 이와 같은 결과는 쥐에 carbofuran 투여 후 PB나 3-MC를 투여함으로써 carbofuran의 대사가 빠르게 이루어지고, 주 대사산물 중3-hydroxycarbofuran보다 독성 이 낮은 3-ketocarbofuran으로의 대사가 빠르게 이루어지기 때문에 carbofuran의 독성이 경감되어 쥐가 생존할 수 있는 것으로 판단된다.

• 농약과학회지
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• 제3권3호
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• pp.27-36
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• 1999

쥐에 있어서 carbamate계 살충제 carbofuran의 독성에 미치는 phenobarbital sodium(PB) 또는 3-methylcholanthrene(3-MC)의 영향과 작용기작을 효소적 측면에서 구명할 목적으로 이들을 단독 또는 조합으로 경구투여 하여 in vivo 효소활성을 조사하였다. Acetylcholinesterase(AChE)와 butyrylcholinesterase(BuCheE)의 효소활성은 carbofuran 3.8 mg/kg을 투여하였을 때 48시간까지 $20{\sim}70%$ 범위의 저해를 보였고, carbofuran과 PB 또는 3-MC를 조합투여하였을 때 효소활성은 초기에 감소하다가 24시간 후에는 대조구와 비슷한 수준을 나타냈다. Glutathione S-transferase(GST)의 경우 carbofuran만을 투여하였을 때 초기($0.5{\sim}6$ hr)에 $15{\sim}35%$의 저해를 보였으나, carbofuran과 PB 또는 3-MC의 조합투여시 초기에는 약간 저해를 보이다가 3시간 후에는 대조군과 유사한 효소활성을 보였고, 6시간 후에는 대조군에 비해 활성이 20%이상 증가하였다. UDP-glucuronosyltransferase(UDPGI) 및 cytochrome P-450 효소계의 효소활성은 carbofuran과 PB 또는 3-MC를 조합 투여하였을 때 투여 후 6시간까지는 carbofuran만의 투여에 비해 효소활성이 $2.6{\sim}2.8$배 이상 높았다. 이상의 결과에서 PB 및 3-MC의 투여가 이들 효소활성을 유도하므로써 carbofuran의 독성으로부터 쥐를 보호한 것으로 판단된다.

• 한국환경성돌연변이발암원학회지
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• 제24권1호
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• pp.40-45
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• 2004

In order to understand the mechanism of the regulation of drug metabolizing enzyme gene expression, we have studied the induction of CYP1A1 and GSTα, μ, π enzymes in Japanese monkey and rhesus monkey after the treatment with 3-methylcholanthrene (3MC) and di-n- butyl phthalate (DBP) and bisphenol A (BPA). The levels of mRNA were measured_by RT-PCR in brain, intestine and liver. In the case of adult monkey, treatment with 3MC induced CYP1A1 mRNA in brain by 2-fold. The treatment with DBP induced CYP1A1 mRNA. Effects of 3MC and DBP on GST mRNA expression was not clear. But GSTμ was slightly inhibited by the treatment with 3MC and DBP. GSTα was not induced by the treatment with 3MC and DBP in brain. GSTπ was slightly induced by the treatment with 3MC and DBP in brain. In the case of fetus monkey, the basal levels of fetus CYP1A1 mRNA and GSTs mRNA were relatively low compared to adult monkey. As the age of monkey increased, the basal levels of CYP1A1 mRNA were also increased. 3MC induced the expression of CYP1A1 mRNA in liver, whereas it didn't significantly induce CYP1A1 mRNA in brain. The levels of GSTμ and GSTα were not changed by the treatment with 3MC and DBP. GSTπ was slightly induced by the treatment with 3MC and DBP.

• 한국환경성돌연변이발암원학회지
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• 제24권2호
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• pp.73-78
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• 2004

In order to understand the mechanism of the regulation of drug metabolizing enzyme gene expression, we have studied the induction of CYP1A1 and GST$\alpha$, $\mu$, $\pi$ enzymes in Japanese monkey and rhesus monkey after the treatment with 3-methylcholanthrene (3MC) and di-n- butyl phthalate (DBP) and bisphenol A (BPA). The levels of mRNA were measured by RT-PCR in brain, intestine and liver. In the case of adult monkey, treatment with 3MC induced CYP1A1 mRNA in liver by 10-fold. The treatment with DBP induced CYP1A1 mRNA. Effects of 3MC and DBP on GST mRNA expression was not clear. But GST$\mu$ was slightly inhibited by the treatment with 3MC and DBP. GST$\pi$ was not induced by the treatment with 3MC and DBP in liver. GST$\alpha$ was slightly induced by the treatment with 3MC and DBP in liver. In the case of fetus monkey, the basal levels of fetus CYP1A1 mRNA and GSTs mRNA were relatively low compared to adult monkey. As the age of monkey increased, the basal levels of CYP1A1 mRNA were also increased. 3MC induced the expression of CYP1A1 mRNA in liver. The levels of GST$\mu$ and GST$\alpha$ were not changed by the treatment with 3MC and DBP. GST$\pi$ was slightly induced by the treatment with 3MC and DBP.

• 한국환경농학회지
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• 제16권1호
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• pp.61-66
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• 1997

본 연구는 carbofuran이 흰쥐의 신장, 간 및 뇌조직내 각종 세포의 미세구조에 미치는 독성을 비교${\cdot}$관찰하고, 더불어 phenobarbital sodium(PB) 및 3-methylcholanthrene(3-MC)이 carbofuran의 독성에 어떠한 보상효과를 갖고 있는지를 밝히고자 각 실험동물에 carbofuran과 PB 및 3-MC 단독 또는 carbofuran과 PB 및 carbofura과 3-MC를 조합 투여한 후 경시적으로 각 조직을 적출하여 광학 현미경으로 관찰을 하였다. 신장에서의 carbofuran단독투여균의 경우 투여후 48시간까지 신장소체의 많은 세뇨관들이 폐쇄되는 독성이 나타났으나 Carbofuran과 PB 또는 3-MC의 조합처리군의 경우 각각 투여후 6시간부터 다소 재생되기 시작하여 48시간 후에는 현저히 회복되는 경향이었다. 간에서의 carbofuran 단독투여군의 경우 투여후 48시간까지 간세포에 퇴행성변화인 괴사 및 심한 변성이 관찰되었으나 Carbofuran과 PB 또는 6시간후부터 간세포들의 재생이 뚜렷하였다. 뇌에서의 carbofuran 단독투여군의 경우 투여후 48시간까지 퇴행성변화 및 대뇌피질의 모세혈관 확장이 나타났으나 Carbofuran과 PB 또는 3-MC의 조합처리군의 경우 투여후 6시간후 이후에는 대조군과 유사하였다. 이상의 결과로 보아 PB와 3-MC 모두 carbofuran에 의한 쥐의 조직독성을 감소시킬수 있는 물질임을 알 수 있었다.

• 한국환경성돌연변이발암원학회지
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• 제24권1호
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• pp.19-24
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• 2004

In order to understand the mechanism of the regulation of drug metabolizing enzyme gene expression, we have studied the induction of CYP1A1 and $GST\alpha,$ $\mu,$ $\pi$ enzymes in Japanese monkey and rhesus monkey after the treatment with 3-methylcholanthrene (3MC) and di-n-butyl phthalate (DBP) and bisphenol A (BPA). The levels of mRNA were measured by RT-PCR in brain, intestine and liver. In the case of adult monkey, treatment with 3MC induced CYP1A1 mRNA in intestine by 11-fold. The treatment with DBP induced CYP1A1 mRNA. Effects of 3MC and DBP on GST mRNA expression was not clear. But $GST\mu$ was slightly inhibited by the treatment with 3MC and DBP. $GST\alpha$ was induced in intestine by 1.5-fold. $GST\pi$ was slightly induced by the treatment with 3MC and DBP in intestine. In the case of fetus monkey, the basal levels of fetus CYP1A1 mRNA and GSTs mRNA were relatively low compared to adult monkey. As the age of monkey increased, the basal levels of CYP1A1 mRNA were also increased. 3MC induced the expression of CYP1A1 mRNA didn't significantly induce CYP1A1 mRNA in intestine. The levels of $GST\mu$ and $GST\pi$ were not changed by the treatment with 3MC and DBP. $GST\pi$ was slightly induced by the treatment with 3MC and DBP.

• Toxicological Research
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• 제17권2호
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• pp.123-129
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• 2001

This study were carried out to investigate cytotoxicity of paraquat and bentazon that is scattering to farm products were essensial for human diet and compensatory effects of 3-methylcholanthrene (3-MC) in vitro and in vivo. In vitro, The 5.0$\times$$10^4$ cell/ml of NIH 3T3 fibroblast in each well of 24 multidish were cultured. After 24 hours, the cells were treated with solution of paraquat and bentazon (1, 25, 50, 100 pM respectively). After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours, Sulfohordamin B Protein (SRB) assay were performed to evaluate the cytotoxicity of cell organelles. Paraquat and bentazon $SRB_50$ were 1860.73 $\mu\textrm{M}$, 1913.38 $\mu$M respectively. In vivo, Sprague Dawley male rats divided into paraquat and bentazon only administered group and simultaneous application group of paraquat and bentazon and 3-MC. At 30 min. and 1, 3, 6, 12, 24, 48 and 96 hrs. interval after each treatment, the animals were sacrificed by decapitation and kidney were immediately removed, immersed in fixatives, and processed with routine method for light microscopic study. Paraffin sections were stained with H-E, PAM, and PAS. Under the light microscope, atrophic change of renal corpuscles were frequently observed from 3 hrs after paraquat and bentazon treatment. The increase of the mesangium was apparent from 12 hrs later after paraquat and bentazon treatment. Necrotic changes of the epithelium and loss of brush border of proximal tubules were most severe at 48 hrs after paraquat and bentazon treatment, respectively. In contrast there were no evidences of the toxic effects on renal tissues at 48hrs in paraquat and bentazon plus 3-MC treated groups.

• Archives of Pharmacal Research
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• 제19권6호
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• pp.514-519
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• 1996

In order to understand the mechanism of action of flavonoids on the drug metabolizing enzyme, cytochrome P450IA1, this study was undertaken to examine the effect of chrysin, morin, myricetin and aminopyrine on the activities of ethoxyresorufin O-deethylase and benzo(.alpha.) pyrene hydroxylase in the liver. In the isolated perfused rat liver that was pretreated with 3-methylcholanthrene (3MC), chrysin, morin, myricetin and aminopyrine inhibited the activity of ethoxyresorufin O-deethylase with concentration dependent manner. The isolated liver perfusion with chrysin, morin, myricetin and aminopyrine showed inhibition on the induction of ethoxyresorufin O- deethylase by 3MC. And also, in mouse liver hepa I cells, 3MC-stimulated the benzo(.alpha.)pyrene hydroxylase activity which was inhibited by chrysin, morin, myricetin and aminopyrine. These results strongly suggested that hydoxylated flavonoids interfered not only the induction of cytochrome P45OIA1 enzymes by 3MC but also the interaction of substrates and enzyme.