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R Thust

Publications and source records attributed to R Thust.

At least 37 records · Page 2Linked to original sources
PubMed1984

[Carcinogen screening in mammalian cells in vitro. The clastogenicity and the SCE test].

A survey is given about problems related to cheking for genotoxicity of environmental chemicals. Cytogenetic effects, induction of structural chromosome aberrations (clastogenicity) and sister chromatid exchanges (SCEs), are very sensitive indicators of genetic damage in eukaryotic cells. Problems and methods of the clastogenicity and SCE assay in mammalian cells in vitro are described. These bioassays are correlation tests and do not allow a definitive prediction of carcinogenic activity of chemicals, but they are a valuable tool for the evaluation of genetic/carcinogenic risks. Problems of extrapolation to man are discussed.

Animals↗
PubMed1983

Genetic and cytogenetic effects of 1,3-dimethyl-3-phenyl-1-nitrosourea in Salmonella typhimurium and Chinese hamster V79 cells.

1,3-Dimethyl-3-phenyl-1-nitrosourea (DMPNU) shows no spontaneous decomposition in aqueous buffered solution (pH 7.0) at 37 degrees C over a measuring period of 10 days, but it is directly genotoxic in all assays applied. This compound induces base substitutions in Salmonella typhimurium (especially in the plasmid harbouring strain TA 100), gene mutations at the HGPRT+ locus of Chinese hamster V79 cells, and is a very potent inducer of clastogenic damage and sister chromatid exchanges in V79 cells. Data on gene mutation induction by 1-methyl-1-nitrosourea are included for comparison. The findings on DMPNU are discussed in comparison with trialkylnitrosoureas. In contrast to these latter compounds, DMPNU is active without addition of S9 mix in vitro. It is assumed that its genotoxic activity is due to an intracellular catalytic degradation favoured by the electron-withdrawing effect of the phenyl group.

Animals↗
PubMed1983

Genotoxicity of Fusarium mycotoxins (nivalenol, fusarenon-X, T-2 toxin, and zearalenone) in Chinese hamster V79-E cells in vitro.

The mycotoxins nivalenol, fusarenon-X, T-2 toxin and zearalenone were checked for clastogenic damage, induction of SCEs and cell cycle delay in Chinese hamster V79-E cells in vitro. The trichothecenes nivalenol, fusarenon-X and T-2 toxin provoked a marked toxicity as especially expressed by cell cycle delay. As compared to toxicity, they are weak clastogens. Addition of S9 mix toxified nivalenol, detoxified T-2 toxin and had no marked influence on fusarenon-X activity. SCE values were slightly increased. It is suggested that the effects observed are unspecific and are caused by inhibition of protein synthesis. Zearalenone was inactive in the three assays. Problems of genotoxicity and carcinogenicity of Fusarium toxins are discussed.

Animals↗
PubMed1983

The carcinogenicity of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU).

In long-term experiments with Hooded rats the carcinogenic potential of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU) could be demonstrated for the first time. Br-MPNU is formed also endogenously after combined administration of 1-methyl-3(p-bromophenyl)-urea (Br-MPU) and sodium nitrite. After repeated intragastric administration of 0.33 mmol Br-MPU and 0.73 mmol NaNO2 per kg b.w. papillomas and carcinomas of the forestomach developed in 83%. After repeated administration of 0.28 mmol Br-MPNU per kg b.w. these neoplasms were observed in 88%. The comparison of results obtained in similar experiments with 1-methyl-3-phenyl-1-nitrosourea shows that bromine substitution led to a reduction of the carcinogenic activity. The present paper is part of a complex program studying the interrelationships between structure, physico-chemical properties, mutagenicity and carcinogenicity of nitrosoureas.

Administration, Oral↗
PubMed1982

Patulin, a further clastogenic mycotoxin, is negative in the SCE assay in Chinese hamster V79-E cells in vitro.

Patulin is a potent inducer of chromatid-type aberrations in Chinese hamster V79-E cells, but loses its activity when 9000 g supernatant of rat-liver homogenate is added. The narrow dose range of patulin clastogenicity shows a quantitative relationship between absolute amount of mycotoxin applied and the number of indicator cells treated. Within a dose range permitting survival of V79-E, patulin does not induce an increase of the SCE rate. It is suggested that patulin clastogenicity is caused by interaction with chromosomal proteins and that DNA is not the virtual target of this mycotoxin.

Animals↗
PubMed1982

Interindividual variation of carcinogen activation by human liver homogenates. A study using dimethylnitrosamine (DMN) and cyclophosphamide (CP) as precursor genotoxic agents and clastogenicity and induction of sister chromatid exchanges in Chinese hamster V79-E cells as endpoints.

9000 g supernatants of liver homogenates from 6 kidney transplant donors were checked in combination with Chinese hamster V79-E cells in vitro for their capacity to activate DMN and CP. 9000 g fractions were standardized on protein content. Induction of chromatid aberrations (clastogenicity assay) and sister chromatid exchanges (SCE assay) served as parameters. DMN activation showed a 1.3-fold inter individual variation and was in the same order of magnitude as that observed with rat liver 9000 g fractions. Striking interindividual differences were found when CP was applied as reference precarcinogen. Most of the samples had a distinctly lower activity than that of the rat but reached, in one case, a similar level. Methodological problems and limitations of genotoxicity tests for precarcinogen screening with respect to extrapolation of results to man are discussed.

Animals↗
PubMed1982

Alkylarylnitrosoureas--stability in aqueous solution, partition coefficient, alkylating activity and its relationship to SCE induction in Chinese hamster V 79-E cells.

The alkylating activity, chemical stability in aqueous solution (pH 7.0; 37 degrees C), and partition coefficient (octanol/water) of the following compounds were determined: 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1-isopropyl-3-phenyl-1-nitrosourea (i-PrPNU), 1-methyl-3-(p-fluorophenyl)-1-nitrosourea (F-MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (Cl-MPNU), 1-methyl-3-(p-bromophenyl)-1-nitrosourea (Br-MPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU), and 1-methyl-3-naphthyl-1-nitrosocarbamate (NCA). 1-Methyl-1-nitrosourea (MNU) and 1-ethyl-1-nitrosourea (ENU) were used for the comparison. THe rate of decomposition in aqueous solution is discussed concerning the influences of the substituents at the 1- and 3-N-atom. The mono- and disubstituted N-nitrosoureas showed a coarse correlation between alkylating activity and SCE induction in Chinese hamster V 79-E cells. On the other hand, this correlation is missing in the case of NCA, which is a potent SCE inducer despite relatively low alkylating activity. DMPNU is the strongest SCE inducer, but this compound shows a high stability in aqueous solution and, consequently, we were not able to detect an alkylating activity.

Alkylating Agents↗
PubMed1981

Clastogenicity and sister chromatid exchange induction by ftorafur.

The main effect of Ftorafur at the chromosomal level is the induction of chromatid and chromosome breaks, which is some pronounced in neoplastic or transformed cells than in normal cells. Different cell lines used in the study exhibited both in vitro and in vivo varying sensitivity to Ftorafur. Ftorafur does not increase the frequency of SCE.

Animals↗
PubMed1981

The influence of sodium selenite on tumor induction by methylnitrosourea (MNU) in rats.

The effect of sodium selenite on tumor induction by MNU was studied in 3 groups of 40 WE rats each. Group I received 10 intraperitoneal injections of 20 mg/kg b. w. MNU in intervals of 4 weeks and beginning with the 1st administration 4 ppm sodium selenite in the drinking water. Rats of group II and III were given only MNU or selenite, respectively. A slight but statistically not significant increase of tumors was found in group I as compared with group II. In group III tumors did not occur. Problems of the anticarcinogenic action of sodium selenite and other antioxidants are discussed.

Animals↗
PubMed1980

Differences in carcinogenicity after transplacental and postnatal administration of drugs and pesticides.

Comparative studies of the carcinogenic activity of procarbazine, methylphenylnitrosourea and ethylenethiourea after transplacental and postnatal administration showed that there were marked differences in frequency and spectrum of tumors induced. Possible causes of these differences are briefly discussed. It is suggested that transplacental experiments can provide special advantages in testing drugs and environmental chemicals for potential carcinogenicity and should be included in test programs.

Animals↗
PubMed1980

Nitrosated urea pesticide metabolites and other nitrosamides. Activity in clastogenicity and SCE assays, and aberration kinetics in Chinese hamster V79-E cells.

The nitrosoureas 1-methyl-1-nitroso-3-phenylurea, 1-ethyl-1-nitroso-3-phenylurea, 1-methyl-1-nitroso-3-(p-fluorophenyl)urea, 1-methyl-1-nitroso-3-(p-chlorophenyl)urea, and 1-methyl-1-nitroso-3-(p-bromophenyl)urea, as well as their non-nitrosated parent compounds, were checked for induction of chromosomal aberrations and sister-chromatid exchanges in V79-E cells without metabolic activation in vitro. For comparison, methylnitrosourea, ethylnitrosourea and nitrosocarbaryl were included in this study. Whereas the non-nitrosated agents were inactive, the nitroso derivatives were potent clastogens and inducers of SCEs. Clastogenicity parallels SCE induction, but the latter assay is about 10 times more sensitive (based on concentration of substance) than the clastogenicity assay. The dependence of aberration frequency on sampling time, which was studied for 5 nitroso compounds, revealed striking differences. As demonstrated by differential chromatid staining, the lag phase until maximal aberration rates may cover more than 2 cell cycles. Preventive oncological aspects of these nitrosamides and the mechanism of aberration kinetics are discussed.

Animals↗
PubMed1980

Physico-chemical, mutagenic and carcinogenic properties of nitrosated urea herbicide metabolites.

Alkylating activities, rates of decomposition, partition coefficients (octanol/water) and sister chromatid exchanges of several N-nitroso compounds, formed by nitrosation of pesticide metabolites or closely related substances, were determined. The carcinogenic activity of two compounds was investigated in rats. The measured parameters were compared in a search for possible correlations.

Animals↗