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아플라톡신을 간회 투여한 랫드의 간에서 CYP450 1A1, p53의 발현과 DNA adduct의 형성
이범준,이숙진,김태명,김대중,남상윤,현상환,강종구,홍진태,김철규,윤영원,Lee, Beom Jun,Lee, Sook Jin,Kim, Tae Myoung,Kim, Dae Joong,Nam, Sang Yoon,Hyun, Sang Hwan,Kang, Jong Koo,Hong, Jin Tae,Kim, Cheul Kyu,Yun, Young Won 대한수의학회 2004 大韓獸醫學會誌 Vol.44 No.4
Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus that grow in improperly stored cereals. Aflatoxin B1 ($AFB_1$) is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of $AFB_1$, the relative toxicity of aflatoxins ($AFB_2$ and $AFG_1$) is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1$, $AFB_2$, and $AFG_1$ at the dose of 250 ${\mu}g/kg$ (additionally including a dose of $1250{\mu}g/kg $ for $AFB_1$) body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin exposure. Subsequently the immunohistochemical examination of p53, cytochrome p450 1A1 (CYP450 1A1), and glutathione-S-transferase placental form (GST-P) were performed. The level of the 8-OxodG in the liver was determined. Expressions of CYP450 1A1 and p53 were high in the liver of rats through 48 hrs after treatment of $AFB_1$ at the single dose of $250{\mu}g/kg $. This pattern was more clear as increasing doses. The treatment of $AFB_2$ and $AFG_1$ did not affect the expression of CYP450 1A1 but it caused weak expression of p53. The activity of GST were not found in the liver of rats treated with aflatoxins. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of control. The treatment of $AFB_2$ and $AFG_1$ did not affect the levels of 8-OxodG in the liver of rats with increasing time. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as CYP450 1A1, p53, GST-P, and 8-OxodG.
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중기 다장기 발암성시험법을 이용한 플라스틱 가소제의 전암단계 병변에 미치는 영향
한범석(Beom Seok Han),박기대(Ki Dae Park),조완섭(Wan Seob Cho),송창용(Chang Yong Song),조현무(Hyun Mo Cho),김철규(Cheul Kyu Kim),최미나(Mina Choi),성낙원(Nak Won Seong),이여진(Yeo Jin Lee),오상연(Sang Yeun Oh),정자영(Jayoung Jeong),김 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.3
This study was conducted to assess the modifying effects of diisodecyl phthalate (DIDP) and diethylhexyl phthalate (DEHP) in the rat medium-term multi-organ bioassay using five different carcinogens. Seventy five, 6-week-old, male F344 rats were divided into four groups. Animals were sacrificed at week 12. To evaluate modifying effects of preneoplastic lesions of DIDP and DEHP, we measured glutathione S transferase placental form (GST-P) and 5-bromodeoxyuridine (BrdU) expression level in liver, numbers of aberrant crypt foci (ACF) in colon and performed histopathological observation. The body weights of rats given 12,000 ppm DEHP and 8,000 ppm DIDP were significantly decreased compared to those of control group. Relative liver and kidney weights of rats given DIDP were significantly increased compared to those of control group in a dose dependent manner. There was no significance of GST-P positive foci and BrdU labeling indices in liver and numbers of ACF in colon among each group. Although hyperplasia of urinary bladder of rat given DEHP were significantly increased compared to that of control group, there were no significant changes of preneoplastic lesions on all organs of rats given DIDP. These results indicate that DIDP has no modifying effect on preneoplastic lesions in all organs.
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장인석,채갑용,강태석,김용규,김철규,황진희,황대연,이주은,허영범,정근기,조정식 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-
수컷 SD 랫드를 사용하여, 핀탄수화물 급여군(HCHO), 탄수화물 및 지방 혼합 급여군(MPAT) 및 고지밟 급여군 (틴FAT), 그리고 절식군(R료I:T) 깊군을 체중웨 따란 완전임의 배치한 후 정제사료를 13주 동안 자옳 급식토록 하였다. 시험결과 체중에서는 절식관인 REST군을 제외하고 운의적 차이가 나타난지 않았으나, 사료 섭취량에서는 고수준의 탄순화물 급여군(HCHO)이 고지방 급여군(딘FAT)에 비해 유의적(P<0.95)으로 증가하였다. 혈중 glucose 함량은 HFAT군에서 다른 군에 비해 유의적으로 증가되었으나,중성지항은 오히려 고탄수왔물 급여군인 HCHO군엑서 증가하는 경향이 뚜렷하였다. 혈장내 insulin 농도는 HFAT군에서 현저한 증가를 보여 insvliu resistauce 현상을 나타내었다. 혈중 leptiBl농고는 MFAT와 HFAT군에서 HCHO와 REST군에 비해 유의적으로 증가하였으며, 특힉 절식군인 REST군에서는 HFAT와 HFAT군들에 비왜 약 3배 이상의 감소치를 보였다. Leptin receptor(extra-cellular와 intracellular donlain)의 mnNA 발현을 조사한 결과 영양소원 및 절식에 따른 영향 즉 혈중 leptin 함량에 따라서 leptin receptor왁 발현은 아문런 차이를 나타내지 않았다. NPY를 시상하부 3곳의 주요 nuclei(arcu-ate, paraventricular, supraopti매에서 면역 염잭하여 관찰한 결과 역시 혈중 leptin 및 insulin 함량파는 상관없이 HC려0, MfAT 및 HFAT군에서 모두 비슷한 양상을 보였다. 그러나 절식군인 REST군에서는 NPY 발현이 감소 하였다. 결론적으로 주에너지원으로 고지방 급여시 비만 및 당뇨가 유발되었으며, 증가된 혈중 leptin 맞 insulin은 41상31부 lertinreceptor 및 NPY조절을 통한 비만 조절 기전에 유의한 영향을 미치지 않았다. Leptin, prodv.cts of the adipose-specific oS gene, acts an important effect in the rrgulation of obesity. Several studies with obesity model animals have suggested that the action of leptin or-erted in the hypothalamus of the brain. However, in contrast to obesity model animals such as oo/oc, dD/08 mice aBd zucker rats,,dietary induced obesity model has not been intensively investigated on leptin'ssignaling pathway. Therefore, six wk old SD rats(n= 90) were allotted to HCHO(high carbohydratediet) group fed the diet couts.ming 70% carbohydrate and 11% fat, Mf'AT (medium fat diet) group frdthe diet containing 48% carbr)hydrate and 32.5% fat, HFAT(high fat diet) group fed the containing 33.3% carbohydrate and 42.8% fat, as basis of energy, and REST(restricted feeding) group that fed 50%restricted amount of ad fiSifHu3 of MFAT diet. All diets except REST consist of the salne energy densityand SB rats tvere continualty fed the purified diets for 13 wks. The body weight was not altered by die-tary treatrnftts eBcept REST group. However, daily feed intake increase4 in HCHO and MFAT grouprcompared with HFAT. Also, feeding HFAT enhanced serum glucose, insulin, and leptin levels when com-pared with IfCHO and REST groups. A second. stage was to determine whether the expressions of leptinreceptor and neuropeptide Y(Iffy ) in the hypothalamos were affected by serum leptin and insulia con-centrations. No difference in leptin receptor mRNA expression by RT-PCR were found amoBg groups. Inaddition, serum leptin and insulin did not alter NPY expression levels in arcuate, paraventricular, andsupraoptic nuclei in the hypothalamus. In summary, the expressions of leptin receptor and NPY arealtered by neither diet, nor leptin and iusulin levels in dietary induced obese SD rats.
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Yoon, Chang Yong,Hong, Choong Man,Cho, Yong Yeon,Song, Ji Young,Song, Hee Jong,Yun, Young Won,Yang, Ki Hwa,Choi, Kwang Sik,Kim, Cheul Kyu 한국수의공중보건학회 2001 예방수의학회지 Vol.25 No.2
Flow cytometry(FCM)를 이용하여 sperm chromatin structure assay(SCSA)를 실시하면 독성물질로 인한 정자세포 발달과정의 변화 양상을 용이하게 관찰할 수 있다. 이 방법은 정상적인 DNA를 가진 세포는 in situ의 인위적변성에 저항성을 갖지만 독성물질에 susceptibility를 가진 DNA는 인위적 자극에 의하여 DNA 구조에 변화가 일어나는 원리를 이용한다. 본 연구에서는 SD랫드에 여러 농도의 Ethylene glycol monoethyl ether(EGEE)를 4주간 강제 경구투여한 후 EGEE가 부고환 및 정관내 정자세포의 chromatin structure에 미치는 영향을 FCM을 이용하여 측정하였다. 실험결과, EGEE의 투여는 부고환 및 정관내에 변성 DNA를 가진 정자세포의 수를 유의하게 증가시켰다. 부고환의 정자세포의 경우, X축 channel의 중심이동 정도를 나타내는 Xt는 큰 변화를 보이지 않았지만 주 세포집단을 벗어난 세포들의 percentage를 나타내는 COMPt는 농도의존적으로 증가하였다(800 mg/kg B.W./day, p<0.01). 정관내 정자세포의 경우, Xt는 농도의존적으로 증가한(100 mg/kg B.W./day, p<0.05; 200∼800mg/kg B.W./day, p<0.01) 반면 COMPt는 200 mg/kg B.W./day에서 최대치를 보였다. 이러한 결과는 EGEE가 랫드정자세포의 유전자 수준에서도 독성을 일으킬 수 있음을 보여주며, 이를 구체적으로 규명하기 위해서는 향후 EGEE에 의 정자세포에 대한 유전독성학적 측면의 연구가 더 이루어져야 할 것으로 사료된다.
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