Dose response study for 1,3-butadiene-induced dominant lethal mutations and heritable translocations in germs cells of male mice. 1998

I D Adler, and J Filser, and H Gonda, and G Schriever-Schwemmer
GSF-Forschungszentrum für Umweltund Gesundheit GmbH, Institut für Säugetiergenetik, Neuherberg, Germany. Adler@GSF.DE

Butadiene (BD) and its metabolites have extensively been studied in the EU sponsored research project "Multi-endpoint analysis of genetic damage induced by 1,3-butadiene and its major metabolites". Within this project a dominant lethal test and a heritable translocation test were performed with male mice to study the dose-response relationships for the respective endpoints. BD concentrations of 130 and 500 ppm were tested in the dominant lethal assay by exposing male mice on 6 h/day for five consecutive days resulting in doses of 3900 and 15,000 ppmh, respectively. Males were mated for four consecutive weeks at a ratio of 1:2 to untreated females. A positive dominant lethal effect was observed in the first mating week in the experiment with 15,000 ppmh but no dominant lethality was found with the lower dose of 3900 ppmh. The present dominant lethal data have to be viewed together with the data already published for a BD dose of 39,000 ppmh (1300 ppm at 6 h/day on 5 consecutive days) [1]. The main difference between results with the highest and the middle dose is that mating weeks one and two (sperm and late spermatids) showed an effect at 39,000 ppmh while only mating week one (sperm) showed an effect at 15,000 ppmh. In the heritable translocation assay, males mice were exposed with a BD dose of 15,000 ppmh and mated for one week to untreated females. Among 434 F1 offspring, we found 5 translocation carriers (1.15% vs. 0.05% in the historical control, p < 0.001). In the previous heritable translocation experiment with a BD dose of 39,000 ppmh of DB exposure, 2.7% of the offspring carried a reciprocal translocation [2]. These data can be used for quantification of genetic risk. The dose response for BD-induced heritable translocations in sperm and late spermatids of mice was linear (Y = 0.05 + 6.9 x 10(-5)X) and a doubling dose of 725 ppmh could be calculated.

UI MeSH Term Description Entries
D007621 Karyotyping Mapping of the KARYOTYPE of a cell. Karyotype Analysis Methods,Analysis Method, Karyotype,Analysis Methods, Karyotype,Karyotype Analysis Method,Karyotypings,Method, Karyotype Analysis,Methods, Karyotype Analysis
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
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
D012098 Reproduction The total process by which organisms produce offspring. (Stedman, 25th ed) Human Reproductive Index,Human Reproductive Indexes,Reproductive Period,Human Reproductive Indices,Index, Human Reproductive,Indexes, Human Reproductive,Indices, Human Reproductive,Period, Reproductive,Periods, Reproductive,Reproductive Index, Human,Reproductive Indices, Human,Reproductive Periods
D002070 Butadienes Four carbon unsaturated hydrocarbons containing two double bonds. Butadiene Derivative,Butadiene Derivatives,Derivative, Butadiene,Derivatives, Butadiene
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females

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