We quantitatively determined direct cytolysis of murine polymorphonuclear leukocytes (PMN) by various antibiotics measuring their release of prelabelled
51 Cr
in vitro. The β-lactam antibiotics ampicillin, carbenicillin, piperacillin, ceftizoxime, cefotiam and latamoxef, the aminoglycoside gentamicin, the macrolide erythromycin, the lincomycin clindamycin, and the chloramphenicol chloramphenicol, were found to cause no cytolysis of PMN within the range of their usual blood concentrations. But the cytolytic concentrations of these drugs were 100 to 1, 000 times higher. Moreover, their cytolytic effects appeared suddenly at certain concentrations. In contrast, the cytolytic effects of the tetracycline minocycline, fosfomycin (fosfomycin), peptides (colistin, polymyxin B), and the polyene amphotericin B on PMN appeared gradually in a dose-dependent manner, and their cytolytic concentrations were over 50 times higher than their usual blood concentrations for antibacterial antibiotics and over 10 times higher for the antifungal antibiotic. The cytotoxic mechanisms of the above two groups also seemed to be different. Anti-neoplasmic antibiotics could be divided into two groups by their cytotoxic effects on PMN. The cytolytic effects mitomycin, bleomycin and pepleomycin were found to be low. In contrast, those of daunorubicin, actinomycin D, doxorubicin and aclarubicin were markedly high and especially the 50% cytolytic concentration of DNR on PMN (PMN
50) was close to the usual blood cocentration. The PMN
5O was in good correlation with the LD
50, one of the general toxicity indices. These results suggest that our PMN
50 is a possible index of toxicity for these drugs.
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