Induction of micronuclei and sister chromatid exchange in mouse splenocytes after exposure to the butadiene metabolite 3, 4-epoxy-1-butene
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TLDR
The genotoxic effects of EB were studied by estimating micronuclei (MN) and sister chromatid exchange (SCE) frequencies in stimulated mouse splenocytes and a weak aneugenic effect was found as well.Abstract:
3,4-Epoxy-1-butene (EB) is one of the main metabolites of 1,3 butadiene, a widely used industrial chemical. The mutagenic potential of 1,3 butadiene and its metabolites have been studied in different test systems. In this work the genotoxic effects of EB were studied by estimating micronuclei (MN) and sister chromatid exchange (SCE) frequencies in stimulated mouse splenocytes. Mice were treated in vivo with various doses of EB (24.4, 48.8 and 73.2 mg/kg). The antikinetochore antibody technique (CREST) was also applied to MN in cytokinesis blocked cells to investigate any possible aneugenic effect. Both MN and SCE frequencies increased after EB treatment. The induced MN resulted mainly from acentric fragments but a weak aneugenic effect was found as well. Cytotoxic effects of EB were observed at the highest dose. The above results, in combination with others on the effect of 1,3 butadiene and its metabolites in somatic and germ cells of mouse and rat as well as in somatic human cells, form a part of the information needed for application of the parallelogram approach and extrapolation to human risk.read more
Citations
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In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring.
M. Hayashi,James T. MacGregor,D.G. Gatehouse,Ilse-Dore Adler,David H. Blakey,Stephen D. Dertinger,G. Krishna,Takeshi Morita,Antonella Russo,Shizuyo Sutou +9 more
TL;DR: It was concluded that successful application of automated scoring by both flow cytometry and image analysis had been achieved, and defined criteria that should be met if automated scoring is employed, and it was not felt appropriate to attempt to define specific recommended protocols for automated scoring at the present time.
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A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins.
TL;DR: There is no convincing evidence that any genotoxic rodent carcinogens or in vivo genotoxins would remain undetected in an in vitro test battery consisting of Ames+MNvit.
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Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic
Diane Benford,P. Michael Bolger,Philip Carthew,Myriam Coulet,Michael DiNovi,Jean-Charles Leblanc,Andrew G. Renwick,Woodrow Setzer,Josef Rudolf Schlatter,B. Smith,Wout Slob,Gary M. Williams,Tanja Wildemann +12 more
TL;DR: In this paper, the authors present the work of an expert group established by the International Life Sciences Institute - European branch (ILSI Europe) to follow up the recommendations of an international conference on risk assessment of compounds that are both genotoxic and carcinogenic: New Approaches.
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Special Issue: Application of the Margin of Exposure (MoE) Approach to Substances in Food that are Genotoxic and Carcinogenic.
Diane Benford,P. M. Bolger,Philip Carthew,Myriam Coulet,Michael DiNovi,Jean-Charles Leblanc,Andrew G. Renwick,R. W. Setzer,Josef Rudolf Schlatter,B. Smith,Wout Slob,Gary M. Williams,Tanja Wildemann +12 more
References
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Identification of aneuploidy‐inducing agents using cytokinesis‐blocked human lymphocytes and an antikinetochore antibody
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Mutagenicity of butadiene and its epoxide metabolites: I. Mutagenic potential of 1,2-epoxybutene, 1,2,3,4-diepoxybutane and 3,4-epoxy-1,2-butanediol in cultured human lymphoblasts.
J.E. Cochrane,Thomas R. Skopek +1 more
TL;DR: The mutagenic potential of the epoxide metabolites of butadiene (BD) was measured at the tk and hprt loci in TK6 human lymphoblastoid cells, and the ability of DEB to induce deletions may be related to its ability to form DNA-DNA and DNA-protein cross-links.
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