Role of heme metabolism in AZT-induced bone marrow toxicity
✍ Scribed by Dr J. D. Lutton; A. Mathew; R. D. Levere; N. G. Abraham
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 423 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0361-8609
No coin nor oath required. For personal study only.
✦ Synopsis
We studied the effects of azidothymidine (AZT) on rat bone marrow heme metabolism and colony growth as determlned by assays of granuiocyte-inacrophage (CFU-GM), erythrold (CFU-E), burst-forming erythrold (BFU-E), and a-aminoievullnic acid synthase (ALAS), the flrst enzyme In the heme pathway. In ail cases, AZT (14.01 pM) was found to be toxic to bone marrow colony growth. When AZT was included In colony asaays, 1 pM resulted in 98-100% Inhlbltlon, whereas lower concentrations (0.01 pM) inhlblted growth by 5& 76%. In addltion, cultures from AZT-treated animals had a marked reduction in colony growth as compared with sham controls. In most cases, hemin M) was found to overcome some of the colony lnhlbitory effects of AZT. Analysis of heme metaboilsm indlcated that ALAS actlvlty was reduced by 71% in bone marrow cells from treated animals. ALAS actlvlty for control was 204 f 33 pM ALA formed/4 x l@ cells/hr, whereas ALAS activity from AZT-treated animals was only 60 f 3 pM ALA tormed/4 x l@ cellshr.
It Is considered that AZT toxicity may be due in par! to a depresalon In the pool of avallable heme, whlch lo required for adequate hematopolesis.