ABSTRACT
The S9 phenobarbital-induced preparations from Albino rats and 6 strains of inbred and outbred Pzh: SFISS mice were tested by an Ames test for their ability to metabolize the two promutagens 2-aminofluorene (2AF) and cyclophosphamide (CP), and to influence the mutagenic activity of the two directly acting mutagens methyl methanesulphonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). 2AF showed a mutagenic activity after incubation with all kinds of microsomal preparations. S9 from B10. mice (Ah+Ah+) was twice as active as that from D2.BN mice (Ah- Ah-). CP was mutagenic exclusively in the presence of S9 from Pzh: SFISS or B10. mice and from rats. Neither fraction deactivated significantly the mutagenicity of MMS. Microsomal preparations from Albino rats and outbred mice were most active in deactivating the mutagenicity of MNNG.
Subject(s)
Liver/metabolism , Mutagens/metabolism , Salmonella typhimurium/genetics , Animals , Biotransformation , In Vitro Techniques , Male , Mice , Mice, Inbred AKR , Mice, Inbred BALB C , Mice, Inbred Strains , Mutagenicity Tests , Rats , Subcellular Fractions/metabolismABSTRACT
Mutagenicity of aminopyrine and of aminopyrine plus nitrite was tested by the micronucleus test in bone marrow of mice and by host mediated mutagenicity assay with mice as host animals and S. typhimurium strain G 46. In parallel the possibility of the protective action of ascorbic acid was studied. Aminopyrine at the dose of 90 mg/kg po when administered to mice together with potassium nitrite induced a significant increase in the frequency of micronuclei in polychromatic erythrocytes and proved to be mutagenic for a Salmonella strain. In both systems mutagenicity of the combination of aminopyrine at this dose plus nitrite was abolished completely by ascorbic acid (373 or 622 mg/kg po). Ascorbic acid neither induced a significant increase in the frequency of micronuclei nor was mutagenic for the strain G 46. A formulation of aminopyrine with ascorbic acid is proposed.
Subject(s)
Aminopyrine/toxicity , Ascorbic Acid/pharmacology , Mutation , Nitrites/toxicity , Aminopyrine/antagonists & inhibitors , Animals , Bone Marrow/ultrastructure , Female , Male , Mice , Mutagenicity Tests , Nitrites/antagonists & inhibitors , Nitroso Compounds/toxicity , Salmonella typhimurium/geneticsABSTRACT
Oxytetracycline hydrochloride, potassium nitrite and a combination of this antibiotic with the nitrite were tested for their mutagenicity in the host-mediated assay with mice as the host animals. The Salmonella typhimurium strain used was his G46. The bacteria were injected intraperitoneally, and the test compounds were administered by a stomach tube. Neither oxytetracycline nor potassium nitrite were mutagenic for strain G46, but the combination of the compounds administered in the highest tolerated doses proved to be mutagenic for this Salmonella strain. The mutagenicity of the compounds was further evaluated by the micronucleus test in the bone marrow of Swiss mice. The test compounds were administered p.o., half the dose 30 h and the rest 6 h before the animals were killed. Oxytetracycline and the combination of oxytetracycline with potassium nitrite induced a significant increase in the frequency of micronuclei in polychromatic erythrocytes. Dose-response experiments with oxytetracycline and with the combination of the antibiotic with nitrite revealed an apparent no-effect level at 2 X 50 to 2 X 500 mg/kg. At higher doses both oxytetracycline and oxytetracycline with nitrite significantly influenced the ratio of erythrocytes to nucleated cells. The findings were compared with data obtained with dimethylnitrosamine included in both kinds of experiment.
Subject(s)
Mutagens , Mutation , Oxytetracycline/toxicity , Animals , Biotransformation , Bone Marrow/drug effects , Cell Nucleus/drug effects , Female , Male , Mice , Mutagenicity Tests , Nitrites/toxicity , Salmonella typhimurium/drug effects , Species SpecificityABSTRACT
Mutagenic activity of Ledakrin in microbial testing as well as its inductive effect on the release of free phages in lysogenic bacteria were compared with its transforming ability in human cell system. It has been found that Ledakrin is highy mutagenic both without metabolic activation and when activated in vivo. Ledakrin induces the release of free phages in E. coli K12(lambda +), but does not transform human fibroblasts in cell cuture in vitro.
Subject(s)
Acridines/toxicity , Mutagens , Nitracrine/toxicity , Animals , Biotransformation , Cell Transformation, Neoplastic , Enzyme Induction , Fibroblasts/drug effects , Humans , In Vitro Techniques , Mice , Nitracrine/metabolism , Salmonella typhimurium/drug effectsABSTRACT
The capability of methotrexate, jododeoxyuridine and 5-fluorouracil to induce lambda prophage was compared when given alone or in combination. All these drugs were found to cause inducing conditions in Escherichia coli K12(lambda) cells. Combined action of jododeoxyuridine and methotrexate resulted in a pronounced increase in the number of free phages compared with that resulting the treatment either with methotrexate of jododeoxyuridine alone. Treatment with 5-fluorouracil caused inactivation of plaque forming ability in cells induced with methotrexate.
