The restriction endonuclease Alu I induces chromosomal aberrations and mutations in the hypoxanthine phosphoribosyltransferase locus, but not in the Na+/K+ ATPase locus in V79 hamster cells.

The restriction endonuclease Alu I induces chromosomal aberrations and mutations in the hypoxanthine phosphoribosyltransferase (HPRT) locus as measured by 6-thioguanine resistance (TGr) in V79 hamster cells. Alu I does not induce mutations in the Na+/K+ ATPase locus as measured by ouabain resistance (OUAr). The data are interpreted to mean that most if not all Alu I-induced TGr mutations represent chromosomal aberrations.

Bacterial mutagenicity of the tranquilizing constituents of Valerianaceae roots.

The valepotriates valtrate/isovaltrate and dihydrovaltrate are considered to be the main tranquilizing constituents of drugs derived from the roots of several Valerianaceae. The decomposition products of valtrate and isovaltrate include the metabolites baldrinal and homobaldrinal, respectively, whereas the decomposition products of dihydrovaltrate do not include baldrinal-like metabolites. Purified valtrate/isovaltrate, dihydrovaltrate, baldrinal and homobaldrinal were investigated for their genotoxic activity in the Salmonella/microsome test and the SOS-chromotest. The valepotriates developed mutagenic activity in these test systems only in the presence of S9 mix, whereas both baldrinals showed mutagenic effects in both tests with and without metabolic activation.

[The mutagenicity of caramel colors]. / Untersuchungen zur Mutagenität von Zuckercouleuren.

In the present study commercially available caustic and ammoniated caramel colours were tested for their mutagenic potential using the Ames assay. The test was performed using the standard test strains Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100 with and without a metabolic activation system (S9-mix). Furthermore, a special preincubation procedure without metabolic activation system was applied. None of the tested caramel colours showed any mutagenic effect in the Ames test.

Formaldehyde-induced sister chromatid exchanges in vitro and the influence of the exogenous metabolizing systems S9 mix and primary rat hepatocytes.

Formaldehyde-induced sister chromatid exchanges (SCE) in vitro and the influence of the exogenous metabolizing systems, S9 mix and primary rat hepatocytes, were studied. The SCE-frequency in V79 cells was dose dependent. A three- to four-fold increase at non-toxic doses was observed. However, in the presence of an exogenous metabolizing system, the number of formaldehyde-induced SCE decreased. S9 mix as well as hepatocytes reduced the SCE frequency to nearly that of the control range. It could be demonstrated that the reduction was not due to an unspecific binding of formaldehyde to macromolecules of the added S9 mix. The decrease in genotoxic effects, due to rapid metabolisation of formaldehyde in vitro and in vivo, explains the differences between results obtained in the in vitro experiments--performed without metabolizing systems--and in vivo results.

[Mutagenicity of meat flavorings with natural and/or nature-identical flavorings]. / Untersuchungen zur Mutagenität von Fleischaromen mit natürlichen und/oder naturidentischen Aromastoffen.

The mutagenic potential of twenty commercially available meat flavours from three different producers was determined using the Ames test. The flavours contained natural and/or nature-identical components as recorded on their label. Twelve flavours showed mutagenic activity with at least one of the four employed test strains (TA1535, TA100, TA97, and TA98). Flavours containing natural components yielded positive results in this mutation test in all cases but one. On the other hand flavours produced from nature-identical substances with one exception did not demonstrate mutagenic effects.

In vitro mutagenicity of valepotriates.

Valepotriates are epoxide-bearing triesters of the monoterpene alcohol 4,7-dimethylcyclopenta-(c)-pyrane isolated from the roots of several Valerianacae species. They are regarded as the main tranquilizing constituents of these drugs. Although the valepotriates valtrate/isovaltrate (VAL) and dihydrovaltrate (DH-VAL) showed a strong alkylating activity against the nucleophilic agent 4-(p-nitrobenzyl)-pyridine (NBP), they were not clearly mutagenic for the strains TA98, TA100, TA1535, and TA1537 of Salmonella typhimurium or for the strains WP2 and WP2 uvrA- of Escherichia coli in the absence of a metabolic activation system (S9-mix). However, the valepotriates were mutagenic for TA100, WP2 and WP2 uvrA- at concentrations up to about 1.0 mumole/plate when S9-mix was added to the test system. With more than 1 mumole/plate the valepotriates were toxic in the presence of a metabolic activation system for all strains tested. The mutagenicity of the valepotriates was inversely related to the protein content of the S9-mix used. The mutagenicity and toxicity of the valepotriates could be inhibited when the S9-mix was preincubated with the esterase inhibitor paraoxon (1 mM) for 5 min before the test compounds and bacteria were added. Therefore, bioactivation of the valepotriates by an enzymatic hydrolysis of their ester groups is considered. This could be proven by activating the valepotriates with purified esterase.

Sister-chromatid exchange in Chinese hamster V79 cells exposed to quindoxin, carbadox and olaquindox.

Quindoxin, carbadox and olaquindox were subjected to the Chinese hamster V79/SCE test. All three compounds demonstrated a dose-dependent increase of SCE frequencies.

Investigation, with the Salmonella/microsome test, of psychopharmaceuticals used in meat production.

Azaperone, acepromazine, xylazine and diazepam were tested for mutagenic activity. To screen these veterinary drugs we used the Salmonella/microsome test on 5 histidine-auxotrophic strains, with and without metabolic activation. Azaperone and xylazine were found to be weakly mutagenic.

Investigation of the butyrophenone tranquilizer azaperone and its main metabolites with the Salmonella/microsome test.

In previous experiments, azaperone was found to be weakly mutagenic, after metabolic activation, in the Ames assay. In this study, we subjected metabolites found in rat and swine to the Salmonella/microsome test. 5 histidine-auxotrophic strains were used. The main metabolites could be classified as weakly mutagenic substances.

Microbiological studies investigation mutagenicity of deep frying fat fractions and some of their components.

In this study, the Salmonella/microsome mutagenicity test according to Ames et al. (Mutation Res. 31:347, 1975) was performed in order to detect possible mutagenicity of oxidized deep frying fat fractions. Furthermore, the mono-, di-, tri- and tetrahydroxyoctadecanoic acids and the hydroperoxide of linoleic acid were investigated as model test substances. The Ames assay was carried out with and without metabolic activation including preincubation and liquid culture procedures as described by Mitchell (Mutation Res. 54:1, 1978). The results show no mutagenic effects for the oxidized fractions of deep frying fats nor for the model test substances. At higher concentrations, however, limited test reliability resulted from direct toxic effects on bacterial growth.