Significance of Furine Salvage in Circumventing the Action of Antimetabolites in Rat Hepatoma Cells1

نویسندگان

  • Yutaka Natsumeda
  • Tadashi Ikegami
  • Edith Olah
  • George Weber
چکیده

The flux activities of de novo and salvage purine synthesis were compared in rat hepatoma 3924A cells in various growth phases. The initial rate assays of [I4C]adenine, ("C]hypoxanthine, and |"C]guanine incorporation yielded Michaelis-Menten kinetics with A'msof 5, 7, and 7 #tM,respectively. After replating plateau phase cells in lag and log phases the activity of purine de novo pathway increased 4.5to 8-fold with a preferential rise in guanylate synthesis, whereas purine salvage activities increased only 1.6to 2.1-fold. However, for the syntheses of IMP, AMP, and GMP, the activities of purine salvage pathways were 2to 7-fold, 5to 28-fold, and 2to 32-fold higher than those of the de novo purine pathway. Treatment of cells with acivicin, an inhibitor of the activity of amidophosphoribosyltransferase, phosphoribosylformylglycinamidine synthase, and GMP synthase, inhibited the flux activities of de novo purine, adenylate, and guanylate syntheses to 37, 73, and 3% of the controls and decreased the concentration of GTP to 42%; the concentra tion of ATP did not change and that of 5-phosphoribosyl 1-pyrophosphate increased 3.1-fold. Under these conditions the activities of salvage syn thesis from hypoxanthine and guanine were enhanced 2.5-fold. Treatment of hepatoma cells with IMP dehydrogenase inhibitors, tiazofurin, ribavirin, and 4-carbamoylimidazolium 5-olate, to block de novo guanylate synthesis accelerated the flux activity of guanine salvage pathway. The higher capacity of purine salvage pathway than that of the de novo one and the further rise of the activity in response to the drugs targeted against the de novo pathway highlight the important role salvage synthe sis might play in circumventing the impact of antimetabolites of de novo purine synthesis in cancer chemotherapy.

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

Expression of CXC Chemokines Gro/KC and SDF-1a in Rat H4 Hepatoma Cells in Response to Different Stimuli

Background: It is now well established that several environmental stress factors cause activation of p38 MAP kinase and JNK in various cell types to produce chemokines. Objective: To investigate the expression of CXC chemokines Gro/KC and SDF- 1a in rat's H4 hepatoma cells in response to heat shock, hyperosmolarity and oxidative stress. Methods: Hepatoma cells were maintained in MEM medium. Cel...

متن کامل

HEPATOMA McARDLE-RH7777 CELLS HAVE THE SAME RESPONSE AS NORMAL RAT HEPATOCYTES TO BOTH DIBUTYRYL-cAMP AND ANTICALMODULINW-7

The effects of cAMP-analogue dibutyryl-cAMP and anticalmodulin W-7 were studied on de novo synthesis and secretion of lipids in cultures of hepatoma McArdle RH7777 cells and normal rat hepatocytes. Dibutyryl-cAMP and W -7 separately caused a significant decrease in the secretion of de novo synthesized triacyl [3H]glycerol in both cultures of McArdle cells and rat hepatocytes. The inhibito...

متن کامل

Differences in Nucleolar Antigens of Rat Liver and Novikoff Hepatoma Ascites Cells1

Antisera to nucleoli of Novikoff hepatoma ascites and normal rat liver cells were produced in rabbits by injection of whole, isolated nucleoli. These antisera have been used to compare the nucleolar antigens that were partially fractionated by differential solubilization from nucleoli. Fourteen antigens were detected by these antisera; ten of these antigens were detected by both antisera. Oucht...

متن کامل

Gene Expression under F8 Promoter Driving In Mouse Hepatoma Cells: A Step towards Gene Therapy of Hemophilia

Background and Objectives: Significant progress has been made in treatment of hemophilia. Ex-vivo gene therapy is going popular due to the capability of this method in using isogenic cells for genetic manipulation and reintroducing them into same host after proliferation. Most gene therapy techniques use viral vectors, which usually harbor a strong and non-specific promoter (e...

متن کامل

Collagen Cell Attachment Protein from Rat Hepatoma Cells1

This paper describes the isolation and partial characteriza tion of a collagen cell attachment protein from the spent culture medium of rat hepatoma cells. When compared with serum fibronectin, this attachment protein differed in several biochem ical parameters. The hepatoma attachment protein was partially purified by adsorbing and eluting from an inorganic gel, mag nesium oxide. Cell adhesive...

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:

دوره   شماره 

صفحات  -

تاریخ انتشار 2006