Enhanced drug-metabolizing capacity within liver adjacent to human and rat liver tumors.

نویسندگان

  • L G Sultatos
  • E S Vesell
چکیده

Cytochrome P-450 content (nmol/g of liver) differed within regions of rat liver according to proximity to intrahepatically implanted Morris hepatoma 7795 or 5123D. Liver adjacent to tumor had higher microsomal cytochrome P-450 content, decreased DNA content (mg/g of liver), and unaltered cytochrome c reductase activity compared to histologically indistinguishable liver far-removed from the tumor. Liver either adjacent to or far-removed from tumor contained markedly more cytochrome P-450 and higher cytochrome c reductase activity but less DNA than transplanted Morris hepatomas 7795 and 5123D that were grown intrahepatically. Compared to intramuscular implants of these same tumors, intrahepatically implanted Morris hepatomas 7795 and 5123D had increased cytochrome P-450 content. Tumor-containing liver from two human subjects revealed regional changes in cytochrome P-450-mediated monooxygenases similar to those observed in rats. These results suggest that histomorphically nontumorous mammalian liver directly adjacent to intrahepatic tumors exhibits previously unsuspected biochemical alterations.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Hepatic drug-metabolizing enzymes in primary and secondary tumors of human liver.

Significant increases in activities of epoxide hydrolase, UDP-glucuronosyltransferase, and glutathione S-transferase, and marked reductions in cytochrome P-450 mixed-function oxidase systems occur in hyperplastic nodules induced in rat liver by chemical mutagens. In contrast, activities of both oxidative (Phase I) and conjugative (Phase II) enzymes are decreased in hepatocellular carcinomas ind...

متن کامل

MICROSOME-MEDIATED BENZO[A]PYRENE-DNA BINDING AND INHIBITION BY CYTOSOLIC FRACTIONS FROM LIVER AND SKIN OF ADULT AND WEANLING RATS

Biotransformation of benzo[a]pyrene (BaP) in the presence of microsomal fractions derived from liver and epiderm of adult and weanling rats was examined. The aim of this study was to evaluate the effect of age on the capacity of two organs in transformation of BaP. Subcellular fractions were prepared from skin and liver by ultracentrifugation and were used as the source of BaP metabolizing enzy...

متن کامل

Increased metabolizing activities of the tricarboxylic acid cycle and decreased drug metabolism in hepatocellular carcinoma.

The aim of this study was to determine the metabolizing activities in the liver of patients with hepatocellular carcinoma (HCC). Thin-layer chromatography autoradioluminography was used to measure metabolizing activities. Succinate-producing activity (SPA) was used as an indicator of metabolizing activity of the tricarboxylic acid (TCA) cycle in mitochondria, and diazepam-N-demethylating activi...

متن کامل

Hepatic Drug-metabolizing Enzymes in Primary and Secondary Tumors of Human Liver1

Significant increases in activities of epoxide hydrolase, UDP-glucuronosyltransferase, and glutathione 5-transferase, and marked reductions in cytochrome P-450 mixed-function oxidase systems occur in hyperplastic nodules induced in rat liver by chemical mutagens. In contrast, activities of both oxidative (Phase I) and conjugative (Phase II) enzymes are decreased in hepatocellular carcinomas ind...

متن کامل

Ethynylestradiol-mediated induction of hepatic CYP3A9 in female rats: implication for cyclosporine metabolism.

Repeated treatment of female rats with the synthetic estrogen ethynylestradiol (EE(2)) increases the formation of the cyclosporine A (CyA) metabolites AM1c and AM9 by 3-fold, whereas the formation of AM1 and AM4N is not significantly enhanced. The formation of all four CyA metabolites was inhibited by greater than 80% by the CYP3A-selective substrate midazolam or polyclonal anti-rat CYP3A IgGs ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 77 1  شماره 

صفحات  -

تاریخ انتشار 1980