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Biomedical subjects

J Mendel

Publications and source records attributed to J Mendel.

29 records · Page 2Linked to original sources
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

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↗
PubMed1981

[Structure-activity relationships in experimental neuro-oncology (author's transl)].

Hitherto more than 40 neurotropic chemical carcinogens have been detected. In part, their structure differs considerably from each other. Structure-activity relationships have not been discovered so far within this group of carcinogens. However, those carcinogens whose presumed ultimate carcinogen is represented by an ethyl or methyl cation showed a stronger prenatal neuro-oncogenic effect of ethyl compounds than the analogous methyl compounds. Contrary to this, the methyl compounds exerted a higher neurotropic activity than the corresponding ethyl compounds in adult animals (table I). These findings were now examined by means of ethyl methanesulphonate (EMS) and methyl methanesulphonate (MMS) in pre- and postnatal experiments in rats. Surprisingly, we yielded opposite results. Neurogenic tumors were produced in 9.4% of the animals by prenatal application of EMS whereas following repeated postnatal EMS injections 82.1% of the rats developed neurogenic neoplasms (tables II, III). Further investigations should clarify whether EMS and MMS represent exceptional chemical carcinogens or whether there are other couples of neurotropic carcinogens that show an activity similar to the alkyl methanesulphonates.

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↗
PubMed1978

Use of human-liver microsomes from kidney-transplant donors for the induction of chromatid aberrations and sister-chromatid exchanges by means of pre-carcinogens in Chinese hamster cells in vitro.

Samples of two human livers taken during operation of kidney donor patients were processed for microsome fractions and used for metabolization of cyclophosphamide (CP) and dimethylnitrosamine (DMN) in combination with the NADPH-generating system. Rat-liver microsomes were checked for comparison. Induction of chromatid aberrations and sister-chromatid exchanges in a newly isolated clone of Chinese hamster fibroblasts served as indicators of activity. Human S-9 fractions standardized on protein content showed strong variations of CP and DMN activation. Whereas liver microsomes of one patient (who also suffered from Gaucher's disease) were highly active for both pre-carcinogens and metabolized DMN at the same level as the uninduced rat-liver microsomes, the S-9 fraction from the second patient failed to activate CP, but was distinctly positive for DMN. It is suggested that samples of liver and other organs of renal transplant donors might be a practicable source of freshly prepared human microsome fractions usable in biochemical, genetic and carcinogenetic studies. Problems concerning the extrapolation of results are discussed.

Biotransformation↗
PubMed1978

Methylnitrosophenylurea--a highly carcinogenic compound.

In vitro, 1-methyl-1-nitroso-3-phenylurea (MNPU) was easily formed from 1-methyl-3-phenylurea (MPU) and sodium nitrite in an acid environment. In rats MNPU showed a strong carcinogenic effect, inducing tumors of the forestomach. MNPU was formed endogenously after combined administration of MPU and nitrite to rats, as indicated by the induction of forestomach tumors. MPU itself was not carcinogenic. In the metabolism of the herbicide 1,1-dimethyl-3-phenylurea (fenuron) MPU resulted as a demethylation product. The possible significance for preventive oncology and the role of MNPU as an environmental carcinogen are briefly discussed.

Animals↗