Cytotoxicity of several marketed antibiotics on mammalian cells in culture.

The cytotoxicity and biochemical effects of several marketed antibiotics on four mammalian cell lines were determined. Several metabolites of clindamycin and several clinically useful anticancer drugs were also included in this study. The four 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 ,pole;'ml, ampicillin, lincomycin and penicillin G were not lethal for L1210 cells, nor had they any significant inhibitory effects on the growth of the other cell lines. Tetracycline was the most cytotoxic antibiotic tested, followed by clindamycin and erythromycin, cephaloglycin, and chloramphenicol. In general, inhibition of cell growth paralleled lethality for L1210 cells. Tetracycline was also found to have 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, however, 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 in terms of the possible relation to pseuclomembranous colitis.