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Comparative mutagenic activity of epoxides derived from 1,3-butadiene
204 quences. During the past 15 years dozens of methods for testing chemical compounds have been developed, validated and put into practice. Recently a search for quicker, more sensitive and cheaper procedures of detecting genetic toxicity has been going on. From a scientific point of view these procedures seem to be quite successful. However, in other respects (e.g. extrapolation of results to humans), short-term tests have created new problems rather than solved old ones. Among scientists there is still a controversy of how much this field contributes to toxicological decision making. The aim of this paper is to discuss the difficulties in translating the results of genetic toxicity tests into practical and meaningful decisions concerning the future of specific chemical compounds.
77 Mattern, I.E., F.P. Olthoff-Smith and B.E. Enger-Valk, Medical Biological Laboratory TNO, 2280 AA Rijswijk (The Netherlands)
Development of a system to analyse mutations at the molecular level, based on recombinant DNA techniques Recombinant D N A techniques are used to develop a relatively simple system for the determination of specific base-pair changes that are induced in DNA by mutagenic agents. This system will be applied in studies on the mechanism of action of mutagenic agents and on the effect of DNA-repair processes on mutation induction. An E. coli plasmid was constructed carrying a mutated trpA gene of E. coli with a known base-pair substitution, leading to an inactive gene product. In the mutated form, the DNA at the site of the mutation is sensitive to a restriction enzyme. Upon reversion to the (pseudo)-wild-type form, this sensitivity is lost but a site is formed instead that is sensitive to another restriction enzyme. T r p - E. coli cells containing this plasmid are treated with the agent to be studied, and Trp + revertants are selected. From these, plasmid DNA is isolated and analysed with the appropriate restriction enzymes for the base-pair change(s) involved in the reversion.
78 de Meester, C., M. Mercier, and F. Poncelet, Laboratory of Toxicology and Food Science, School of Pharmacy, UCL-73, Avenue E. Mounier, 1200 Brussels (Belgium)
Comparative mutagenic activity of epoxides derived from 1,3-butadiene Previous investigations have demonstrated that 1,3-butadiene (BUT) is mutagenic towards the strains of Salmonella typhimurium sensitive to base-pair substitution. The mixed-function oxidase system is responsible for the metabolic activation step.
77 Mattern, I.E., F.P. Olthoff-Smith and B.E. Enger-Valk, Medical Biological Laboratory TNO, 2280 AA Rijswijk (The Netherlands)
Development of a system to analyse mutations at the molecular level, based on recombinant DNA techniques Recombinant D N A techniques are used to develop a relatively simple system for the determination of specific base-pair changes that are induced in DNA by mutagenic agents. This system will be applied in studies on the mechanism of action of mutagenic agents and on the effect of DNA-repair processes on mutation induction. An E. coli plasmid was constructed carrying a mutated trpA gene of E. coli with a known base-pair substitution, leading to an inactive gene product. In the mutated form, the DNA at the site of the mutation is sensitive to a restriction enzyme. Upon reversion to the (pseudo)-wild-type form, this sensitivity is lost but a site is formed instead that is sensitive to another restriction enzyme. T r p - E. coli cells containing this plasmid are treated with the agent to be studied, and Trp + revertants are selected. From these, plasmid DNA is isolated and analysed with the appropriate restriction enzymes for the base-pair change(s) involved in the reversion.
78 de Meester, C., M. Mercier, and F. Poncelet, Laboratory of Toxicology and Food Science, School of Pharmacy, UCL-73, Avenue E. Mounier, 1200 Brussels (Belgium)
Comparative mutagenic activity of epoxides derived from 1,3-butadiene Previous investigations have demonstrated that 1,3-butadiene (BUT) is mutagenic towards the strains of Salmonella typhimurium sensitive to base-pair substitution. The mixed-function oxidase system is responsible for the metabolic activation step.