Cytotoxicity of several marketed antibiotics on mammalian cells in culture

Li, L.H.; Kuentzel, S.L.; Shugars, K.D.; Bhuyan, B.K.

The Journal of Antibiotics 30(6): 506-512


DOI: 10.7164/antibiotics.30.506
Accession: 068515764

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The cytotoxicity and biochemical effects of several marketed antibiotics on 4 mammalian cell lines were determined. Several metabolites of clindamycin and several clinically useful anticancer drugs were studied. The 4 cell lines were mouse leukemia L1210, human oral carcinoma KB, human acute myelogenous leukemia RPMI 6410 and human lymphocyte RPMI 1788. At concentrations of 0.4 .mu.mole/ml, ampicillin, lincomycin and penicillin G were not lethal for L1210 cells and had no significant inhibitory effects on growth of other cell lines. Tetracycline was the most cytotoxic antibiotic tested, followed by clindamycin and erythromycin, cephaloglycin and chloramphenicol. Inhibition of cell growth paralleled lethality for L1210 cells. Tetracycline apparently had a stronger inhibitory effect than clindamycin on DNA, RNA and protein synthesis in human RPMI 6410 cells. Drug effects on macromolecular synthesis correlated closely to those on cell growth. Among the clindamycin metabolites, clindamycin sulfoxide and clindamycose were nontoxic and only N-demethyl clindamycin had an activity equivalent to that of clindamycin. The structure-activity relationships of these metabolites are briefly discussed. None of the antibiotics tested, with the possible exception of tetracycline approached the potency exhibited by most anticancer drugs. The lack of potential for these antibiotics as anticancer drugs is discussed. The biological and biochemical effects on mammalian systems observed with clindamycin are discussed with possible relation to pseudomembranous colitis.