Localization of CYP1A1 and CYP1A2 messenger RNA in normal human liver and in hepatocellular carcinoma by in situ hybridization
Localization of CYP1A1 and CYP1A2 messenger RNA in normal human liver and in hepatocellular carcinoma by in situ hybridization
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通过原位杂交定位正常人肝脏和肝细胞癌中的 CYP1A1 和 CYP1A2 信使 RNA
作者：
R. Mckinnon;P. Hall;L. Quattrochi;R. Tukey;M. McManus
为了更好地表征CYP1A基因产物在人体中的精确细胞分布，我们对人肝脏中的CYP1A表达进行了北方印迹和原位杂交分析。用从CYP1A1和CYP1A2互补DNA转录的核糖核酸探针对23个人肝信使RNA样品进行一系列北方印迹，在11个样品中证实了CYP1A1表达，在22个样品中证实了CYP1A2表达。这些肝脏中两种CYP1A酶的表达水平表现出明显的变异性。然后使用CYP1A1和CYP1A2核糖探针在石蜡包埋、福尔马林固定的人肝切片上进行CYP1A1/1A2信使RNA序列的原位杂交定位。这些研究表明，CYP1A1和CYP1A2信使RNA在人肝腺泡中分布不均匀，在终末肝小静脉和闰静脉周围的肝细胞中水平最高。抗兔CYP1A1血清的免疫组织化学显示了翻译的CYP1A蛋白的相应分布。还对肝细胞癌切片进行了原位杂交分析，证明CYP1A表达显著下调。在艾姆斯试验中，使用食物源性杂环胺MeIQ（2-氨基-3，4-二甲基咪唑并[4，5-f]喹啉）活化为诱变剂作为CYP 1A表达指标的功能研究证实了这种下调。这些结果证明了个体之间和不同腺泡区中肝脏CYP1A表达的异质性。这种表达的变化可能在评估各种药物和致癌物的细胞特异性毒性方面具有重要意义。（Hepatology 1991; 14：848 - 856）。
To better characterize the precise cellular distribution of CYP1A gene products in man, we have undertaken Northern‐blot and in situ hybridization analyses of CYP1A expression in human liver. Using riboprobes transcribed from both CYP1A1 and CYP1A2 complementary DNAs to probe a series of Northern blots of 23 human liver messenger RNA samples, CYP1A1 expression was demonstrated in 11 samples and CYP1A2 expression was evident in 22 samples. The level of expression of both CYP1A enzymes in these livers demonstrated marked variability. The CYP1A1 and CYP1A2 riboprobes were then used for in situ hybridization localization of CYP1A1/1A2 messenger RNA sequences on paraffin‐embedded, formalin‐fixed human liver sections. These studies demonstrated that both CYP1A1 and CYP1A2 messenger RNAs are distributed nonuniformly across the human liver acinus, with levels highest in hepatocytes surrounding terminal hepatic venules and intercalated veins. Immunohistochemistry with an anti‐rabbit CYP1A1 serum demonstrated a corresponding distribution for the translated CYP1A proteins. In situ hybridization analysis was also performed on sections of hepatocellular carcinoma, demonstrating a significant down‐regulation in CYP1A expression. Functional studies using the activation of the food‐derived heterocyclic amine MeIQ (2‐amino‐3,4‐dimethylimadazo [4,5‐f] quinoline) to a mutagen in the Ames test as an indicator of CYP1A expression confirmed this down‐regulation. These results demonstrate heterogeneity of hepatic CYP1A expression both between individuals and in different acinar zones. This variation in expression may be of significance in assessing cell specific toxicities of various drugs and carcinogens. (HEPATOLOGY 1991;14:848–856).
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对未经治疗的大鼠肝脏内苯巴比妥和 3-甲基胆蒽诱导细胞色素 P-450 的定位和分布进行免疫组织化学研究。
DOI：
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发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Baron,J;Redick,JA;Guengerich,FP
通讯作者：
Guengerich,FP
DOI：
10.1073/pnas.86.20.7696
发表时间：
1989-10-01
影响因子：
11.1
作者：
BUTLER, MA;IWASAKI, M;KADLUBAR, FF
通讯作者：
KADLUBAR, FF
人肝微粒体细胞色素 P-450 酶参与鼠伤寒沙门氏菌 TA 1535/pSK1002 中 Umu 基因反应检测到的原致癌物的生物激活。
影响因子：
11.2
作者：
Shimada,T;Iwasaki,M;Martin,MV;Guengerich,FP
通讯作者：
Guengerich,FP
鉴定与大鼠体内主要异黄樟素诱导型细胞色素 P-450 同源的人肝细胞色素 P-450。
影响因子：
3.6
作者：
Wrighton,SA;Campanile,C;Thomas,PE;Maines,SL;Watkins,PB;Parker,G;Mendez-Picon,G;Haniu,M;Shively,JE;Levin,W
通讯作者：
Levin,W
与编码 P-450 4 和 P-450 6 的二恶英诱导兔 mRNA 同源的人细胞色素 P-450 cDNA 的克隆和分离。
DOI：
10.1089/dna.1985.4.395
发表时间：
1985
期刊：
DNA (Mary Ann Liebert, Inc.)
影响因子：
--
作者：
Quattrochi,LC;Okino,ST;Pendurthi,UR;Tukey,RH
通讯作者：
Tukey,RH