Evaluation of genotoxicity of ampicillin and carbenicillin on human lymphocytes in vitro: chromosome aberrations, mitotic index, cell cycle kinetics, satellite associations of acrocentric chromosomes and sister chromatid exchanges.
A large number of drugs have been introduced into man's environment in recent years, many of which have been shown to have mutagenic, teratogenic and carcinogenic effects. Keeping in view the potential hazardous effects of drugs and chemicals, it is desirable to test new drugs for their genotoxic effects prior to widespread use. In the present investigation genetic effects of ampicillin and carbenicillin were studied in vitro in human lymphocytes using a number of end-points. These drugs were added at a range of concentrations and times during a 72h culture period. Concentrations corresponding to the plasma level after receiving therapeutic doses as well as concentrations higher than the plasma levels were examined. Neither drug affected the frequency of chromosome aberrations, satellite associations, mitotic index and cell turnover rate at plasma level concentrations. However, all these parameters were affected at higher concentrations. The frequency of SCEs was not increased with both the drugs irrespective of the concentrations or durations of treatment, suggesting that the mechanisms leading to the formation of SCEs and chromosome aberrations are different. Both ampicillin and carbenicillin were genetically non-toxic for the end points measured and non-clastogenic in vitro at therapeutic doses. However, previous studies have shown ampicillin to be clastogenic in vivo. For evaluation of genetic toxicity, drugs should be tested both in vitro and in vivo.
D000328:Adult; D000667:Ampicillin / Q000633:toxicity*; D002228:Carbenicillin / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002503:Centromere / Q000187:drug effects; D002869:Chromosome Aberrations; D003434:Crossing Over, Genetic / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008940:Mitotic Index / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000667:Ampicillin; D002228:Carbenicillin