Comparison of the mutagenic activity of dialkylnitrosamines in animal-mediated and in vitro assays using an Escherichia coil indicator

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Abstract
An intrasanguineous host-mediated assay was used to establish the mutagenic potential of a series of dialkylnitrosamines to E. coli K12/343/113 in the liver and spleen of mice. For calibrating purposes, dose-and time-dependent kinetics of mutation induction by the model compound diethylnitrosamine in this assay was determined. Comparison with the results of the same compound in vitro reveals that activation in the intact liver of living mice is more efficient and proceeds for a longer period of time than during incubation in the presence of a liver homogenate. The mutagenicity of five other dialkylnitrosamines (dimethyl-, diethanol-, diisopropyl-, methylethyl-, and methyl-n-propylnitro-samine) was also determined. The results of host-mediated assays in livers and spleens of mice indicate a good correlation with the carcinogenic properties of these compounds as far as the effect on the liver is concerned. The mutagenic activity in vitro shows, however, a poor correlation with carcinogenicity data, mainly because some of the carcinogenic nitrosamines are not detectable in those tests. It is concluded that, under the present experimental conditions, intrasanguineous host-mediated assays are more sensitive and more representative of the carcinogenic activity of dialkylnitrosamines than in vitro assays using S-9 liver fractions.

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