THE MYELOTOXICITY OF CHLORAMPHENICOL - IN-VITRO AND IN-VIVO STUDIES -II - IN-VIVO MYELOTOXICITY IN THE B6C3F(1) MOUSE

1 Chloramphenicol continues to be widely used in many parts of the wor ld despite its known haematotoxicity. Until mow, elucidation of the me chanisms involved and any attempt al amelioration of the toxic effects have been hampered by the lack of an animal model. 2 Ire this study n either acute nor chronic administration of chloramphenicol as its succ inate ester in the drinking water produced anaemia in mice as assessed by changes in peripheral blood parameters. 3 Chloramphenicol could nu t be detected in the bone marrow when the antibiotic was administered either in the drinking water or by gavage, although it was detected in fins serum. 4 In marrow taken from mice after chloramphenicol succina te administration and cultured in vitro, depression of the differentia tion of immature committed erythroid progenitors occurred 15 min after administration of a-he antibiotic by gavage. However, recovery was be ginning to occur at 48 h after administration of chloramphenicol succi nate at 50 and 200 mg/kg and this was then followed by an 'overshoot' response at the higher dose, A toxic effect was therefore achieved in the bone marrow but this was probably masked in the peripheral blood b y enhanced proliferation. 5 Morphological evidence of apoptosis tvas s een in erythroid and myeloid precursors in mice treated with 200 mg/kg . 6 The data suggest that the effect of chloramphenicol was at the dif ferentiation stage of the committed marrow progenitor cells rather tha n at the replication stage of the stem cells and therefore this respon se appears to mimic the reversible bone marrow depression seen in the treated patient.