Mutagenicity studies with nitrofurans. I. Mutagenicity of nitrofurylacrylic acid for mammals. 1979

R J Srám, and P Rössner, and V S Zhurkov, and I Kodýtková

Cytogenetic analysis of mouse bone-marrow cells, the dominant lethal test in mice and the cytogenetic analysis of human peripheral lymphocytes in vitro were used to study the mutagenicity of 3-(5-nitro-2-furyl)acrylic acid (5-NFA) for mammals. The bone-marrow cytogenetic analysis was performed in female mice exposed to 5-NFA administered intraperitoneally in single doses of 15--120 mg/kg and in 5 repeated doses of 15 and 30 mg/kg, intragastrically in single doses of 30--240 mg/kg and 5 repeated doses of 30 and 60 mg/kg, and perorally for 12 weeks to 5-NFA concentration of 10, 100 and 1000 mg 5-FNA/1 in drinking water. The bone-marrow analysis was performed in this case after 12 days, 3, 4, 6, 8, 10 and 12 weeks exposure. No increase in chromosome damage attributable to dosing with 5-NFA occurred in any of these experiments. Experiments in which mice were exposed to 5-NFA in drinking water for 12 weeks and then treated with a single i.p. dose of 2 mg of the mutagen TEPA [trix-(1-aziridinyl)phosphine oxide] per kg revealed that, at a concentration of 1000 mg 5-NFA/1, the clastogenic activity of TEPA was reduced to that in untreated animals. The dominant lethal test was performed in male mice exposed to 5-NFA applied intraperitoneally in single doses of 40--120 mg/kg and in 5 repeated doses of 10--30 mg/kg, intragastrically in 5 repeated doses of 20--60 mg/kg, and perorally for 4 weeks in drinking water containing 5-NFA at concentrations of 10, 100, 316 and 1000 mg/l. No significant differences were detected between the exposed and control groups of animals. Experiments in which male mice were exposed to 5-NFA in drinking water and treated after the 4-week exposure to 5-NFA with 1 mg TEPA/kg revealed that a concentration of 1000 mg 5-NFA/1 reduced TEPA-induced dominant lethality to within control values. A reduction in male fertility was observed after the single or repeated 5-NFA doses, but no changes when 5-NFA was applied in drinking water. The cytogenetic analysis of human peripheral lymphocytes exposed in vitro for the last 24 h of culture to concentrations of 1--100 micrograms 5-NFA/Ml did not show any compound-related chromosomal changes. The results of dominant-lethal and bone-marrow cytogenetic studies in mice after consumption of drinking water containing 1000 mg of 5-NFA/1 for 12 weeks and dosed subsequently with TEPA suggests that 5-NFA has some antimutagenic activity. Because none of the studies reported revealed any compound-related genetic activity, the results suggest that 5-NFA is not a chromosome-breaking agent in mammals.

UI MeSH Term Description Entries
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008297 Male Males
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009581 Nitrofurans Compounds containing FURANS attached to a nitro group.
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D004327 Drinking Behavior Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. Behavior, Drinking,Behaviors, Drinking,Drinking Behaviors
D005260 Female Females
D005799 Genes, Dominant Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state. Conditions, Dominant Genetic,Dominant Genetic Conditions,Genetic Conditions, Dominant,Condition, Dominant Genetic,Dominant Gene,Dominant Genes,Dominant Genetic Condition,Gene, Dominant,Genetic Condition, Dominant

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