Mutagenicity of antibiotics in microbial assays. Problems of evaluation.
5 antibiotics, 4 of which inhibit protein synthesis in different ways, and 1 of which inhibits bacterial cell-wall synthesis, were tested in a battery of microbial assays for possible genetic effects. All the antibiotics, chloramphenicol, tetracycline, gentamicin, oleandomycin and phosphonomycin induced forward mutation to L-azetidine-2-carboxylic acid resistance in Escherichia coli WP2. This response was closely correlated with the toxic effects and was inferred to be deletion mutation. In addition, chloramphenicol was weakly active in reversion of the frame-shift mutation in Salmonella typhimurium TA98, gentamicin caused petite induction in S. cerevisiae at pH 4.4--4.7 and tetracycline gave a significant reponse with gene conversion and petite induction also in S. cerevisiae but at pH 7.2. The results, particularly those with E. coli, cast doubts on the validity of testing specifically designed antibacterial agents in bacteria, and raise serious problems in the evaluation of such data in terms to human populations.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000494:pharmacology*; D002872:Chromosome Deletion; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects; D005578:Fosfomycin / Q000494:pharmacology*; D005785:Gene Conversion; D005839:Gentamicins / Q000494:pharmacology*; D008862:Microsomes, Liver; D009152:Mutagenicity Tests; D009827:Oleandomycin / Q000494:pharmacology*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity; D013752:Tetracycline / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D005578:Fosfomycin; D002701:Chloramphenicol; D013752:Tetracycline; D009827:Oleandomycin