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SE Steinberg, CL Campbell, PS Rabinovitch and RS Hillman
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 microgram/ml and S 40 microgram/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, 08 microgram/ml; S, 4
microgram/ml) cell growth was less markedly inhibited, morphology remained
megaloblastic, and S-phase block was still dramatic. A further tenfold
reduction (T, 0.08 microgram/ml; S, 0.4 microgram/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.
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