CHEMOSENSITIVITY TO TRIAZENE COMPOUNDS AND O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE LEVELS - STUDIES WITH BLASTS OF LEUKEMIC PATIENTS

被引：63

作者：

DATRI, S

PICCIONI, D

CASTELLANO, A

TUORTO, V

FRANCHI, A

LU, K

CHRISTIANSEN, N

FRANKEL, S

RUSTUM, YM

PAPA, G

MANDELLI, F

BONMASSAR, E

机构：

[1] UNIV ROMA TOR VERGATA, DEPT EXPTL MED & BIOCHEM SCI, ROME, ITALY

[2] ROSWELL PK CANC INST, BUFFALO, NY USA

[3] UNIV ROMA TOR VERGATA, DEPT INTERNAL MED, ROME, ITALY

[4] UNIV ROMA LA SAPIENZA, DEPT BIOPATHOL, ROME, ITALY

[5] CNR, INST EXPTL MED, ROME, ITALY

来源：

ANNALS OF ONCOLOGY | 1995年 / 6卷 / 04期

关键词：

ALKYLTRANSFERASE; CHEMOSENSITIVITY; LEUKEMIA; TRIAZENES;

D O I：

10.1093/oxfordjournals.annonc.a059189

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: A clinical pilot study performed by our group showed that dacarbazine can induce a marked reduction of blast cells in patients with acute myelogenous leukaemia (AML). Leukaemic blasts (LB) from responsive patients showed low levels of O-6-alkylguanine-DNA alkyltransferase (OGAT). Design: An in vitro study was performed to evaluate OGAT levels and sensitivity to temozolomide (a triazene compound that spontaneously decomposes into the active metabolite of dacarbazine) in a relatively large number of LB samples. Results: OGAT levels varied widely among the LB of different patients, with a mean value higher in acute lymphoblastic leukaemias than in AML. About 25% of LB obtained from patients with AML showed low OGAT activity, in the range corresponding to that observed in leukaemic patients responsive to dacarbazine in vivo. A reasonable inverse correlation was found between OGAT levels and LB sensitivity to temozolomide. Conclusions: Triazenes could have a therapeutic potential in human leukaemias. Moreover, OGAT determination could provide rapid and reliable information about a patient's susceptibility to these antitumor agents.

引用

页码：389 / 393

页数：5

共 40 条

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