An assessment of chloramphenicol and thiamphenicol in the induction of aplastic anaemia in the BALB/c mouse.
The potential of the antibiotics chloramphenicol succinate (CAPS) and thiamphenicol (TAP) to induce aplastic anaemia in the female BALB/c mouse was investigated. CAPS was administered at 2000 mg/kg, and TAP at 850 mg/kg, daily by gavage, for 17 days. At 1, 13, 22, 41, 98 and 179 days after the final dose of each antibiotic, mice (n = 4 or 5) were sampled for haematological examination and haematopoietic stem cell assays. Both CAPS and TAP induced significant reductions in red blood cell count, haematocrit and haemoglobin values at day 1 post dosing; counts of colony-forming units-erythroid and colony-forming units-granulocyte-macrophage, were similarly significantly decreased at this time. All these reduced parameters returned towards normal at days 13 and 22. At days 41, 98 and 179, results for all haematological values and stem cell assays in both CAPS- and TAP-treated mice compared with the controls; there was no evidence of a reduction in peripheral blood values or bone marrow parameters at the later sampling points, as would be expected in a developing or overt bone marrow aplasia. We therefore consider that the administration of CAPS and TAP, which have been associated with the development of aplastic anaemia in man, induce a reversible anaemia, but not a chronic bone marrow aplasia, when given at haemotoxic dose levels for 17 days in the BALB/c mouse.
Turton
J A
JA
Centre for Toxicology, Department of Pharmacology, The School of Pharmacy, University of London, UK. turton@cua.ulsop.ac.uk
Havard
A C
AC
Robinson
S
S
Holt
D E
DE
Andrews
C M
CM
Fagg
R
R
Williams
T C
TC
D000741:Anemia, Aplastic / Q000097:blood / Q000139:chemically induced*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002701:Chloramphenicol / Q000633:toxicity*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D023461:Myeloid Progenitor Cells / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D013839:Thiamphenicol / Q000633:toxicity*; D013997:Time Factors
D011500:Protein Synthesis Inhibitors; D002701:Chloramphenicol; D013839:Thiamphenicol