title: The effect of trimethoprim/sulfamethoxazole on Friend erythroleukemia cells.
abstract: 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.
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004911:Erythrocyte Volume / Q000187:drug effects; D005622:Friend murine leukemia virus; D002955:Leucovorin / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000097:blood*; D008534:Megaloblasts / Q000187:drug effects; D013420:Sulfamethoxazole / Q000494:pharmacology*; D014295:Trimethoprim / Q000494:pharmacology*
chemical_list: D004247:DNA; D014295:Trimethoprim; D013420:Sulfamethoxazole; D002955:Leucovorin