The Effect of Trimethoprim/Sulfamethoxazole on Friend Erythroleukemia Cells

Cultures of Friend erythroleukemia cells were subjected to the antibiotics trimethoprim (T) and sulfamethoxazole (S) at levels equal to or below the usual therapeutic range. At T 8 µg/ml and S 40 µg/ml, cell growth was arrested, cells appeared megaloblastic, and the examination of cell-cycle distrib...

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Bibliographic Details
Published in:Blood 1980-03, Vol.55 (3), p.501-504
Main Authors: Steinberg, S.E., Campbell, C.L., Rabinovitch, P.S., Hillman, R.S.
Format: Article
Language:English
Subjects:
Cell Transformation, Neoplastic - drug effects
Cells, Cultured
DNA - analysis
Dose-Response Relationship, Drug
Erythrocyte Volume - drug effects
Friend murine leukemia virus
Leucovorin - pharmacology
Leukemia, Erythroblastic, Acute - blood
Megaloblasts - drug effects
Sulfamethoxazole - pharmacology
Trimethoprim - pharmacology
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Summary:Cultures of Friend erythroleukemia cells were subjected to the antibiotics trimethoprim (T) and sulfamethoxazole (S) at levels equal to or below the usual therapeutic range. At T 8 µg/ml and S 40 µg/ml, cell growth was arrested, cells appeared megaloblastic, and the examination of cell-cycle distribution by flow microfluorimetry revealed arrest in S phase. With a tenfold reduction in drug levels (T, 0.8 µg/ml; S, 4 µg/ml) cell growth was less markedly inhibited, morphology remained megaloblastic, and S-phase block was still dramatic. A further tenfold reduction (T, 0.08 µg/ml; S, 0.4 µg/ml), well below effective antibacterial levels, allowed normal cell growth and morphology but DNA synthesis was still inhibited. Additions of folinic acid at 100 ng/ml averted all drug effects. Thus, T/S can affect cell replication even at levels well below those usually employed and could prolong the rate of recovery of hematopoietic cells in the myelosuppressed patient.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V55.3.501.501