Biomedical subjects

V Mersch-Sundermann

Publications and source records attributed to V Mersch-Sundermann.

At least 37 records · Page 2Linked to original sources

PubMed1995

[Antimicrobial oligopeptides--an important factor in non-specific defense against infection].

For survival of plants, animals as well as main in a nature full of aggressive microbes, endogenous antibiotics play an essential role, which is not yet fully appreciated in medicine and science. For example in the granules of polymorphonuclear granulocytes and macrophages or even of specialized epithelial cells such as Paneth cells in the crypts of the intestinal mucosa, oligopeptides are produced with a wide range of antimicrobial activity. According to their chemical structures and modes of action they can be grouped into various different families. The physiological role of these agents on the surface of skin and mucosa or within host tissue is only incompletely understood.

Bacteria↗

PubMed1994

The structural basis of the genotoxicity of nitroarenofurans and related compounds.

The CASE (Computer-Automated Structure Evaluation) methodology has been applied to an investigation of the basis of the genotoxicity (sfiA induction) of 79 nitroarenofurans and related molecules examined with the E. coli PQ37 genotoxicity assay (SOS chromotest). CASE identified 9 major activating structural fragments (biophores) responsible for the probability of genotoxicity (SAR). With respect to quantitative features, CASE identified 8 major molecular subunits related to the genotoxic potency (QSAR). Both the SAR as well as the QSAR analysis indicate that a nitro group on position 2 of the furan ring is important for activity provided one or more aromatic rings are attached to the furan ring, i.e. 2-nitrobenzofuran, 2-nitronaphthofuran, 2-nitroanthrafuran and 8-nitropyrenofuran. Additionally, a small substituent at position 3 of the furan ring, i.e. the methyl group of R7371, the ethyl group of R7427 and the butyl group of R7429, enhance the activity of 2-nitronaphtho[2,1-b]furan (R6597), whereas longer aliphatic chains decrease activity. Moreover, the activity of the nitro group at position 2 of the furan ring was increased by substitution of a methoxy group at position 7 of the R6597 structure. Additionally the n-octanol/water partition coefficient (log P) was found to be an important descriptor for the genotoxic potency in E. coli PQ37. Using the identified descriptors CASE correctly predicted the probability of genotoxicity of all of the genotoxicants and non-genotoxicants in the data base. The calculated genotoxic potency was equally good: 94% of all predicted results were within plus/minus one order of magnitude of the experimental result. Using CASE in the predictive mode, the program correctly predicted the probability of sfiA induction in E. coli of 95.8% of 24 "unknown" nitroarenofurans which were not part of the learning set (QSAR with r = 0.88-0.97).

Benzofurans↗

PubMed1994

SOS induction in Escherichia coli and Salmonella mutagenicity: a comparison using 330 compounds.

To examine the concordance of two microbial genotoxicity short-term assays, 330 experimental results for the SOS chromotest using tester strain Escherichia coli PQ37 were compared with the results of the Salmonella/mammalian microsome mutagenicity assay with Salmonella typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and/or TA1538. With respect to qualitative features, the concordance between SOS chromotest and Salmonella mutagenicity test results was 86.4% (sensitivity, 78.6%; specificity, 100%; chi 2 = 188.6). None of the non-mutagens (N = 120) were able to induce the SOS system. Additionally, 45 of the 210 S.typhimurium mutagens (21.5%) did not induce the SOS repair system. On closer examination, the majority of these 45 compounds (84%) were mutagens with activities between 0.001 and 10 rev/nmol. Even though the experimental protocols of both systems were not standardized, the correlation coefficient for the experimental results of the two test systems was 0.7 for the 330 chemicals. Except for aliphatic epoxides (r = 0.47), the mutagenicity/SOS induction correlations for congeneric data sets (polycyclic aromatic hydrocarbons, nitroarenes, nitroarenofurans, mycotins) were even better (r = 0.72-0.95). Additionally, computer automated structure evaluation (CASE) analyses of the nature of the structural determinants associated with each endpoint indicate extensive homologies. The data can be taken to indicate that the two phenomena reflect common mechanisms of action.

Animals↗

PubMed1993

Influence of S9 mix composition on the SOS response in Escherichia coli PQ37 by polycyclic aromatic hydrocarbons.

To investigate the variability in test results obtained with the SOS chromotest (Escherichia coli PQ37 genotoxicity assay) when varying the composition of the exogenous metabolizing system (S9 mix), we examined the influence of different S9 and NADP concentrations, of buffer pH value, of SDS concentrations, the effects of E. coli PQ37 density and centrifugation steps on the expression of beta-galactosidase (beta g) and alkaline phosphatase (ap) activity, the calculated induction factors (IFs) and SOS-inducing potencies (SOSIPs). Additionally we examined the metabolic potency (stability) of S9 mix when stored at 37 degrees C before use. Initially, we used 0-5000 ng (= 0-20 nmole) benzo[a]pyrene (B[a]P) as a reference compound for the test procedure in the presence of standard S9 mix. Subsequently, to evaluate the results of S9 mix variations we examined several polycyclic aromatic hydrocarbons (PAHs) using both the standard and a modified S9 mix composition and test protocol. We observed the highest beta g and ap activities and/or IFs using only 11-27 microliters 9000 x g liver supernatant (S9) from Aroclor 1254-induced rats per assay (20-50% of standard amount) and calibrating the S9 mix Tris buffer to pH 7.8-8.0. 60-300 micrograms NADP/assay (10-50% of standard) was sufficient for optimum activation of PAHs. In contrast to previous investigations about the variability of the SOS chromotest in the absence of a metabolizing system, higher induction factors were obtained when using higher bacterial densities (12-18 x 10(6) cfu/assay). Centrifugation steps as recommended by other investigators were not necessary when using optimum S9 amounts. The metabolic activity of S9 mix remained nearly constant approximately 20 min after preparation, but decreased to 80% of its activity in about 1 h.

Animals↗

PubMed1993

The influence of culture conditions on the susceptibility of Salmonella typhimurium in the Salmonella mutagenicity test.

To determine the variability of tester strain susceptibility in the Salmonella mutagenicity assay and to optimize the culturing procedure we examined the influences of the overnight culture period (12-16 h), the use of an additional short-term culturing procedure (1-4 h) and the Salmonella density (cfu/plate) on the rate of revertants per plate. As tester strains we used Salmonella typhimurium TA97, TA98, TA100 and TA102. As shown previously for other microbial genotoxicity short-term tests (i.e. with Escherichia coli PQ37), we observed the highest susceptibility of the Salmonella strains, i.e. the highest amounts of revertants per plate, when using a 12 h overnight culture followed by a 2 h short-term culturing procedure. We calibrated the bacterial count to 100 x 10(6) cfu per assay by photometric measurement (600 nm). Initially, we used 0-1 nmole 2,4,7-trinitro-9-fluorenone with S. typhimurium TA97, 0-15 nmole daunomycin with strain TA98, 0-25 nmole sodium azide with strain TA100 and 0-15 nmole methylmethanesulfonate with strain TA102 as reference compounds in the standard plate incorporation test. Subsequently, to evaluate the results of the culturing procedure variations we examined 22 well-known mutagenic and direct-acting (-S9-mix) compounds out of different chemical classes using both the standard and a modified culturing procedure. The comparison of these results showed a 64% (for 4-nitroquinoline-N-oxide) to 421% (for sodium azide) increased amount of revertants for the modified test protocol.

Colony Count, Microbial↗

PubMed1993

[Ecology and causality--on the reliability of environmental medicine knowledge].

In principle, environmental medicine has two responsibilities. On the one hand this special field is required to provide a practicable and enlightening medicine for people seeking help. On the other hand environmental medicine as an ecological medicine" is required to analyse the truth content in science and the reliability of scientific knowledge with regard to environmental processes. For not only direct-acting toxicities of environmental chemicals but also the imbalance in ecological systems possess pathogenic potencies. Do these ecological processes in systems actually have the demanded obvious causality?

Disease↗

PubMed1992

Structural requirements for the induction of the SOS repair in bacteria by nitrated polycyclic aromatic hydrocarbons and related chemicals.

The CASE (computer-automated structure evaluation) methodology was used to investigate the structural basis of the SOS-inducing activity of 56 nitrated polycyclic aromatic hydrocarbons (nitroarenes, nPAH) and the unsubstituted parent PAH molecules. Based upon the presence and/or absence of structural features, CASE identified 5 activating (biophores) and 4 inactivating (biophobes) fragments responsible for the SOS-inducing activity. Based upon these fragments, CASE correctly calculated the genotoxicity of 94.6% of the molecules in the training set (sensitivity = 0.85, specificity = 1.0). Disregarding the questionable experimental results of the unexpected very weak direct-acting activity of the unsubstituted benzo[a]pyrene, dibenzo[a,h]anthracene and 7,12-dimethylbenz[a]anthracene, the concordance of the prediction was 100%, i.e., sensitivity = 1.0, specificity = 1.0. Additionally, the quantitative analysis of the SOS-inducing potency showed a good correlation between the experimental and predicted results. The present analyses indicate an identity in the structural determinants responsible for SOS induction in E. coli PQ37 (SOS chromotest) and mutagenicity in Salmonella typhimurium.

Computer Simulation↗

PubMed1992

Genotoxicity of polycyclic aromatic hydrocarbons in Escherichia coli PQ37.

In the present investigation, 32 polycyclic aromatic hydrocarbons (PAHs) were tested for genotoxicity in E. coli PQ37 using the standard tube assay of the SOS chromotest. PAHs such as benzo[ghi]fluoranthene, benzo[j]fluoranthene, benzo[a]pyrene, chrysene, dibenzo[a,l]pyrene, fluoranthene and triphenylene exhibited high genotoxicity when incubated in the presence of an exogenous metabolic activation mixture. The results were compared to those obtained with the Salmonella/microsome test.

Alkaline Phosphatase↗

PubMed1992

Structural basis of the genotoxicity of polycyclic aromatic hydrocarbons.

The Computer Automated Structure Evaluation (CASE) system has been applied to investigate the structural basis of the genotoxicity of 37 polycyclic aromatic hydrocarbons examined with the Escherichia coli PQ37 genotoxicity assay (SOS chromotest). CASE identified eight activating and one inactivating structural fragments responsible, for the probability and three activating and one inactivating fragment responsible for the potency of the activity (P less than or equal to 0.15). The present analysis indicate that the main activating fragments identified by CASE were similar to the descriptor for the bay (or modified bay) and K region of PAHs. Using these fragments the computer correctly predicted the probability of genotoxicity of 93.6% of the known genotoxicants and nongenotoxicants in the database. Moreover, the concordance between prediction and experimental results for molecules not in the learning set is greater than 78%.

Animals↗

PubMed1991

Genotoxicity of nitrated polycyclic aromatic hydrocarbons and related structures on Escherichia coli PQ37 (SOS chromotest).

To determine the genotoxicity of nitrated polycyclic aromatic hydrocarbons and related molecules (nPAH) we examined 24 compounds representative of nitroanthracenes, nitrofluorenes, nitronaphthalenes, nitropyrenes, and nitroquinolines for genotoxicity in Escherichia coli PQ37 (SOS-chromotest). To enhance the sensitivity of the tester strain and optimize metabolic activation we used a modified test protocol and S9-mix composition. All chemicals with the exception of 9-nitroanthracene, 1- and 2-nitronaphthalene, 2-methyl-1-nitronaphthalene, and 5-, 6-, and 8-nitroquinoline induced the SOS system of E. coli PQ37. As expected from previously referred mutagenicity studies, the highest SOS inducing potencies (SOSIP) were exhibited by the dinitropyrenes (SOSIP = 151-416), 4-nitroquinoline-N-oxide (SOSIP = 62), and 3-nitrofluoranthese (SOSIP = 16). Except for some nitronaphthalenes, the nPAHs showed their highest genotoxicity in the absence of an exogeneous metabolic activation system. The results were compared to those reported for the bacterial mutagenicity of these substances in Salmonella typhimurium TA98.

Escherichia coli↗

PubMed1991

Sources of variability of the Escherichia coli PQ37 genotoxicity assay (SOS chromotest).

To determine the variability in test results obtained with the Escherichia coli PQ37 genotoxicity assay (SOS chromotest) when varying the test protocol, we examined the influences of sodium dodecylsulfate (SDS) concentrations, of buffer pH and composition on the enzyme assays, the effects of E. coli PQ37 density and culture conditions on the expression and/or determination of alkaline phosphatase (ap) and beta-galactosidase (beta-g) activities, the calculated induction factors (IF) and the SOS-inducing potentials (SOSIP). Initially, we used 0-190 ng (0-1 nmole) 4-nitroquinoline-1-oxide (4-NQO) as a reference compound for the standard procedure in the absence of metabolic activation. Subsequently, to evaluate the results of protocol variations we examined several mutagenic compounds of differing chemical classes using both the standard and a modified assay procedure. We observed the highest enzyme activities using 1 mg SDS per tube and calibrating the ap buffer to pH 8.05 and the beta-g buffer to pH 7.75. The longer the incubation period, the higher the enzyme activities. However, with respect to IF and SOSIP there is no reason to incubate in excess of 90 min. We found no significant differences in the IF and SOSIP values when varying substrate conversion times. There was, however, a definite decrease in beta-g activity when extended substrate incubation times were used. Higher enzyme activities are obtained when the bacterial count is increased. Using lower bacterial counts the enzyme activities decreased, but the sensitivity of E. coli towards genotoxic compounds increased.

4-Nitroquinoline-1-oxide↗

PubMed1991

[Methods and knowledge--the necessity for a system-oriented environmental medicine].

Despite the marked signs that human interventions and manipulations of the natural environment are dangerous to human health, physicians are not very interested in correlations between diseases and changes of the global environment. Physicians and scientists of the medical faculties of the universities as well as residents and general practitioners mostly ignore ecological effects on human life. The reason for this is not only insufficient education, but in particular a wrong theoretical basis with regard to the explanations of global biological and ecological processes. The present paper is supposed to point to the major problems of environmental medicine and the necessity of broader and more detailed scientific knowledge to recognise the multidimensional nature of kinetic and evolutionary systems.

Ecology↗

PubMed1991

The SOS-Chromo-spottest: evaluation of a short-term test for the determination of genotoxic compounds in contaminated environmental samples.

To evaluate the sensitivity of the SOS-Chromo-spottest towards genotoxic compounds 5 reference chemicals (4-nitroquinoline-1-oxide (4-NQO), methylmethansulfonate (MMS), 2,4,7-trinitro-9-fluorenone (TNF), sodium azide (SA) and daunomycin (DM) were tested by 3 different agar plate media (STA-plates: synthetic media containing Xgal, B-plates: synthetic media containing 1% lactose and bromocresolpurple, C-plates: 1% lactose bromocresolpurple media containing complex nutrients). Even 1 ng of 4-NQO showed genotoxic effects by using STA-plates. The threshold value for MMS was 80 nl, for TNF 160 ng and for DM 80 ng. Similarly the spottest with B-plates are positive results, but the sensitivity of this test procedure was 80 to 250 times lower than the STA-plate test. The C-plate test only reacted with high amounts of 4-NQO (1000 ng). Therefore, the SOS-chromo-spottest with STA-media described by Quillardet and Hofnung seems to be a sufficient procedure to detect genotoxic compounds in contaminated environmental samples directly without previous extraction procedures. The simpler B-plates can be used to examine the genotoxicity of certain compounds like industrial or household chemicals where the genotoxicants can be expected to be present in high doses.

4-Nitroquinoline-1-oxide↗

PubMed1989

[The mutagenicity of organic microcontamination in the environment. II. The mutagenicity of volatile organic halogens in the Salmonella microsome test (Ames Test) with regard to the contamination of groundwater and drinking water].

To determine the sensitivity and specificity of microbial shortterm-tests for the registration of the mutagenic potency of halogenated hydrocarbons (OHV) 18 pure substances out of the groups of halomethanes, -ethanes and -ethylenes were examined with different laboratory methods (classical Ames-Test, Spot-Testing, Preincubation-Procedure) of the Salmonella-Microsome-Test (Ames-Test). The Salmonella typhimurium- strains TA97, TA98, TA100 und TA102 were used with and without metabolic activation of Arochlor 1254 induced rat-liver microsomes. Mutagenicity with one or several procedures shows 1,1,2,2-tetrachloroethane, hexachloroethane, trichloroethylene, bromdichloromethane and bromoform without metabolic activation and dichloromethane, tetrachloromethane, 1,1,2,2-tetrachloroethane, hexachloroethane, 1,1-dichloroethylene, trans-1,2-dichloroethylene, tetrachloroethylene and bromdichloromethane with metabolic activation. The range of sensitivity amounted from microgram to nanogram values of OHV's per plate, so that the Ames-test can be a sensitive screening method sufficient for detection of mutagenic effects by several OHV's in high contaminated environmental samples even without extraction procedures.

Fresh Water↗

PubMed1989

[Environment, knowledge and preventive medicine. 1. The ecotoxicologic system model].

Especially in the area of public health organisations are many questions about the medical valuation of environmental pollutions. Now the complicated coherences between environment and health contains great problems on scientific investigations. With the aid of an ecological model of environmental systems it is possible to estimate effects of anthropogene pollutions. The aim is the development of a sufficient health protection program.

Animals↗

PubMed1989

[The environment, knowledge and preventive medicine. 2. Reductionism and holism--a dichotomy in thinking].

The usual theories and methods of biological sciences and medicine are of important rank to valuate the potential risks of environmental pollutions. Because in notice of the represented system model the consideration of ecotoxicological processes shows, that a complete assessement of these risks and the effects of environmental pollutions against human health can only be attainable when holostic mode of thinking is integrated.

Environmental Pollution↗

PubMed1989

[The environment, knowledge and preventive medicine. 3. The radical approach of conservative medicine--preventive environmental medicine as the physician's responsibility].

To develop a strategy of environmental medicine it is necessary to harmonize the scientific and the holistic ways of thinking. On the basis of a holistic philosophy it is possible to set up a constructive system of values that looks ahead and the assessment of anthropogenic pollutions of the environment. It is imperative to change the way of thinking.

Environmental Pollutants↗

PubMed1989

[The mutagenicity of organic microcontamination in the environment. III. The mutagenicity of selected herbicides and insecticides in the SOS chromotest].

To determine the mutagenicity of selected herbicides and insecticides we examined 26 pure pesticide substances (polychlorinated alicyclic hydrocarbons, phenoxy fatty acids, triazines) with the help of SOS-Chromotest. We used Escherichia coli strain PQ37 in these tests without and with metabolic activation with Aroclor 1254 induced rat liver microsome fraction. None of the substances showed a provable induction of the E. coli-SOS-system, because a great number of the pesticides showed toxic effects against bacteria in high concentrations.

Animals↗