Reversal of resistance to methotrexate in L1210 murine leukemia by uracil.

نویسندگان

  • H Wallerstein
  • L M Slater
  • B Eng
  • N Calman
چکیده

BDF1 mice bearing L1210 leukemia, when treated with a regimen of uracil and methotrexate, show an increase in survival time greater than when treated with methotrexate alone. The uracil and methotrexate regimen also delays the development of methotrexate resistance as L1210 leukemia is transferred with therapy through multiple generations of mice. When uracil is applied to multiple generations of mice bearing tumor resistant to methotrexate, there is a return to sensitivity to methotrexate. It is also noted that uracil blocks the responsiveness of L1210 leukemia to 6-mercapto-

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

Cytotoxicity of 5-fluoro-2'-deoxyuridine: requirement for reduced folate cofactors and antagonism by methotrexate.

Protein in vitro inhibition of thymidylate synthase (5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) by 5-fluoro-2'-deoxyuridylate requires 5,10-methylenetetrahydrofolate. The cytoxicity of 5-fluoro-2'-deoxyuridine towards cultured L1210 mouse leukemia cells is reduced when intracellular reduced folates are depleted, either by limiting the source in media or by inhibition ...

متن کامل

Biochemical correlates of responsiveness and collateral sensitivity of some methotrexate-resistant murine tumors to the lipophilic antifolate, metoprine.

The M5076 murine "ovarian" tumor which is naturally refractive to methotrexate was found to be highly responsive to the lipophilic antifolate, metoprine. M5076 cells were markedly deficient in mediated entry of methotrexate. This was in contrast to the L1210 leukemia, a tumor highly responsive to methotrexate but poorly responsive to metoprine. Two L1210 leukemia sublines, with acquired resista...

متن کامل

Evaluation of ribonucleoside and deoxyribonucleoside triphosphate pools in cultured leukemia cells during exposure to methotrexate or methotrexate plus thymidine.

Continuous exposure to inhibitory concentrations of methotrexate produces distinct rates of steady-state growth of murine leukemia L1210 and human leukemia CCRF-CEM cells in culture. Addition of thymidine to the medium produces reversal (6 to 40%) of this steady-state growth rate inhibition. This study utilized combinations of methotrexate and thymidine for an evaluation of the accompanying rel...

متن کامل

The effects of antibiotics and cancer chemotherapeutic agents on the cellular transport and antitumor activity of methotrexate in L1210 murine leukemia.

The effect of the simultaneous addition of a number of clinically useful antibiotics and cancer chemotherapeutic agents on the transport of 2 x 10~6 M methotrexate (4-amino-lO-methylpteroyl-glutamic acid; MTX) was stud ied in L1210 murine leukemia cells in vitro. The results were correlated with the effects of these agents on the antitumor activity of MTX in BALB/cAnN x C57BL/KaLwN F, mice bear...

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:
  • Blood

دوره 38 5  شماره 

صفحات  -

تاریخ انتشار 1971