This study characterizes 21 wastewater samples collected from Al-Amal hospital between the period of 12 April till 8 July 2020. Al Almal is a hospital that provides drug addiction and psychological treatment to patients. Using solid-phase extraction and liquid chromatography with tandem mass spectrometry (LC-MS/MS), chemical contaminants profiles in these wastewater samples were determined in a non-targeted manner. These chemicals were then individually analyzed in an in-silico manner by checking against databases and literature to determine if they were mutagenic. By determining the proportion of mutagenic chemicals against the non-mutagenic ones, we aim to determine if untreated hospital wastewater may potentially negatively impact the downstream municipal biological wastewater treatment process. It was determined that 64% of the identified chemicals were not tested for their mutagenic effect, and hence no prior information is available in the literature and databases. Instead, we further performed in-vitro mutagenicity tests using Ames test to determine if the wastewater sample, with all of its chemical constituents, would be mutagenic. Ames test results showed that majority of the samples were non-mutagenic except for 1 sample that imposed a mutagenic effect on Salmonella enterica serovar Typhimurium TA98 and 3 samples with mutagenic effect on TA100. In addition, 1 sample showed a toxic effect on TA100. However, in all 5 instances, these samples only imposed a mutagenic and toxic effect at high concentrations of > 10x. The findings in this study suggest that a specialty hospital like Al Amal does not contribute substantially to mutagenic wastewater streams to the municipal sewer, and hence unlikely to significantly perturb the downstream biological treatment processes. However, there may still be a need to consider ad-hoc contributions of mutagenic and/or toxic wastewater streams from the hospitals.

Analyzing and modeling data is a well established research area and a vast variety of different methods have been developed over the last decades. Most of these methods assume fixed positions of data points; only recently uncertainty in data has caught attention as potentially useful source of information. In order to provide a deeper insight into this subject, this thesis concerns itself with the following essential question: Can information on uncertainty of feature values be exploited to improve in silico modeling? For this reason a state-of-art random forest algorithm is developed using Matlab R. In addition, three techniques of handling uncertain numeric features are presented and incorporated in different modified versions of random forests. To test the hypothesis six realworld data sets were provided by AstraZeneca. The data describe biochemical features of chemical compounds, including the results of an Ames test; a widely used technique to determine the mutagenicity of chemical substances. Each of the datasets contains a single uncertain numeric feature, represented as an expected value and an error estimate. Themodified algorithms are then applied on the six data sets in order to obtain classifiers, able to predict the outcome of an Ames test. The hypothesis is tested using a paired t-test and the results reveal that information on uncertainty can indeed improve the performance of in silico models.

<p>Analyzing and modeling data is a well established research area and a vast variety of different methods have been developed over the last decades. Most of these methods assume fixed positions of data points; only recently uncertainty in data has caught attention as potentially useful source of information. In order to provide a deeper insight into this subject, this thesis concerns itself with the following essential question: Can information on uncertainty of feature values be exploited to improve in silico modeling? For this reason a state-of-art random forest algorithm is developed using Matlab R. In addition, three techniques of handling uncertain numeric features are presented and incorporated in different modified versions of random forests. To test the hypothesis six realworld data sets were provided by AstraZeneca. The data describe biochemical features of chemical compounds, including the results of an Ames test; a widely used technique to determine the mutagenicity of chemical substances. Each of the datasets contains a single uncertain numeric feature, represented as an expected value and an error estimate. Themodified algorithms are then applied on the six data sets in order to obtain classifiers, able to predict the outcome of an Ames test. The hypothesis is tested using a paired t-test and the results reveal that information on uncertainty can indeed improve the performance of in silico models.</p>

Made available in DSpace on 2014-06-11T19:27:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-12Bitstream added on 2014-06-13T20:56:35Z : No. of bitstreams: 1 oliveira_aps_me_arafcf.pdf: 946584 bytes, checksum: 6c4fbb82549dc1046e8b7771847a8f5b (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A família Eriocaulaceae possui cerca de 1200 espécies divididas em 10 gêneros e suas espécies de plantas são conhecidas como sempre-vivas, por sua grande durabilidade e coloração paleácea. Neste trabalho foram estudadas as espécies: Eriocaulon ligulatum, Leiothrix flavescens e Leiothrix spiralis, as quais foram avaliadas quanto à mutagenicidade e estrogenicidade e algumas substâncias isoladas foram utilizadas para um estudo de relação estrutura-atividade mutagênica e estrogênica. Para avaliação da mutagenicidade, utilizou-se o teste de Ames, e o teste RYA (Recombinant Yeast Assay) foi o empregado para avaliação da estrogenicidade. Os resultados da atividade mutagênica demonstraram que apenas E. ligulatum foi considerado mutagênico e isso foi atribuído às isocumarinas e flavonóides agliconas. Os estudos de relação estrutura-atividade mutagênica mostraram que esta ação foi devida à presença de hidroxilas em posições estratégicas e à ausência de glicosilações, metoxilações, ou qualquer outro tipo de substituição. Para complementar os estudos de relação estrutura-atividade mutagênica com as isocumarinas, utilizou-se resultados já publicados de mutagenicidade de moléculas semelhantes à isocumarina eriocaulina, isolada de E. ligulatum. Verificou-se que os dímeros de isocumarinas têm a sua mutagenicidade influenciada pela conformação espacial, pela presença de grupos hidroxilas mais afastados de grupos volumosos, e pelo tipo de ligação que une os seus monômeros. Quando o potencial estrogênico foi avaliado, apenas a L. flavescens apresentou resultados positivos e que esses são devidos à presença de flavonas agliconas, como a luteolina e a metoxiluteolina. As mesmas isocumarinas, pertencentes a outras espécies da família Eriocaulaceae, avaliadas no teste de Ames, foram avaliadas no teste RYA... / Eriocaulaceae family comprises around 1200 species, divided into 10 genera, and their plant species are known as “sempre-vivas” (everlasting flowers) for its durability and color. In this work the species Eriocaulon ligulatum, Leiothrix flavescens and Leiothrix spiralis were studied. These species were evaluated for the mutagenic and the estrogenic potential and some of their isolated compounds were used for a study of structuremutagenic and estrogenic activities. To assess mutagenicity we used Ames test and the Recombinant Yeast Assay (RYA test) was used for evaluation of estrogenicity. The results of mutagenic activity showed that only E. ligulatum presented mutagenicity and that these results were due to its naphthopyranones and flavonoid aglicons. The structuremutagenic activity studies shown that this action were due to the presence of hydroxyl groups in strategic positions and no glycosylations, methoxylation or any type of substitutions. To complement the studies of structure-mutagenic activity with the naphthopyranones, we use results already published of the mutagenicity of similar compounds to the naphthopyranone eriocaulina, isolated from E. ligulatum, and compare them with the data from ericauline. It was found that the dimers of naphthopyranones have their mutagenicity influenced by its spatial conformation, for the presence of hydroxyl groups furthest away from large groups, and the type of connection that join their monomers. When the estrogenic potential was assessed, we found that only L. flavescens showed positive results and that these results are due to the presence of flavones in the form of aglycones, such as luteolin and methoxyluteolin. The same naphthopyranones belonging to other species of Eriocaulaceae family, evaluated in the Ames test, were assessed in the RYA test. Their results were crucial for the establishment of structureestrogenic activity... (Complete abstract click electronic access below)

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Martina Klaučová Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Consultant: PharmDr. Ivona Pávková, Ph.D. Diploma thesis title: Ames test in the drug development Background: Thesis objective is the determination of potential genotoxicity of newly developed drugs within primary testing and the introduction of the Ames microfluctuation test which can be used in common laboratory conditions. Methods: I used commercially supplied kit based on the principles of Ames test which detects reverse mutation through colour changes of the samples using bacterial strains S. typhimurium. At first I had to study literary sources and then I could design the procedures of the Ames microfluctuation test, preparation of the chemicals and storage of the strains which are optimal for all laboratories. Results: The drug samples T6445 and T6447 with 30 µM concentration tested by metabolic activation S9 on bacterial strain ST TA 98 show genotoxicity. The sample UOCHB1 with 30 µM concentration tested without activation shows possible genotoxicity on both strains ST TA 98 and ST TA 100. Other samples do not show any toxicity. I used 3 different procedures during the designation of assay. The most suitable version of the...

No / Telomerase-targeted strategies have aroused recent interest in anti-cancer chemotherapy, because DNA-binding drugs can interact with high-order tetraplex rather than double-stranded (duplex) DNA targets in tumour cells. However, the protracted cell-drug exposure times necessary for clinical application require that telomerase inhibitory efficacy must be accompanied by both low inherent cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time, the genotoxicity of a number of structurally diverse DNA-interactive telomerase inhibitors is examined in the Ames test using six Salmonella typhimurium bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage induced by each agent was also assessed using the Comet assay with human lymphocytes. The two assay procedures revealed markedly different genotoxicity profiles that are likely to reflect differences in metabolism and/or DNA repair between bacterial and mammalian cells. The mutational spectrum for a biologically active fluorenone derivative, shown to be mutagenic in the TA100 strain, was characterised using a novel and rapid assay method based upon PCR amplification of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary analysis indicates that the majority (84%) of mutations induced by this compound are C→A transversions at position 2 of the missense proline codon of the hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone agent gave a negative response in the Comet assay, and demonstrates how unwanted systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or ameliorated through suitable molecular fine-tuning of a candidate drug in targeted human tumour cells. / CAEB, Balearic Islands and Yorkshire Cancer Research

Mutageniciteten för olika ämnen bestäms vanligtvis med hjälp av konventionella in vivo och in vitro metoder. Att övergå till in silico metoder vore både etiskt och miljö- mässigt gynnsamt. Flera olika parametrar kan användas för att förutse mutagenicitet. Bland dessa ingår energin för lägsta oockuperade molekylorbitalen (LUMO), aktiveringsenergin, lokala min/max i elektrostatiska potentialen (Vs,min/Vs,max), lokala min i ”electron attachment energy” (Es,min ), med flera. Aktiveringsenergin är en parameter som kan förutspå mutagenicitet med hög noggrannhet, förutsatt att reaktionsmekanismen antingen är känd eller kan antas. Däremot är beräkningskostnaden för aktiveringsenergin hög. Mutagen-X (MX) och dess analoger (föreningar med samma grundstruktur men olika funktionella grupper, totalt 29 olika föreningar), är föreningar vars mutagenicitet har bestämts med hjälp av traditionella metoder men har nyligen också kunnat bestämmas genom kvantkemiskmodellering. Kvantkemiskmodellering har med framgång implementerats i studien av Kari Tuppurainen [1]; där LUMO har bestämts för MX och dess analogier. Utöver detta visades även en statistiskt signifikant korrelation mellan LUMO för MX och dess analoger och den biologiska aktiviteten som bestämdes med hjälp av Ames test. Målet med detta arbete har varit att undersöka vare sig mutageniciteten för MX och dess analogier kan även bestämmas genom att beräkna Es,min, Vs,max och aktiveringsenergin. Reaktionen som undersöktes var en Michael additionsreaktion  mellan amingruppen på kvävebasen guanin och betapositionen på MX och dess analogier. Av den anledningen utvärderades parametrarna (Es,min, Vs,max och aktiveringsenergin) vid betapositionen. De beräknade värdena för Es,min var korrelerade med biologiska aktiviteten. Även aktiveringsenergierna för MX och dess analogier beräknades vid betapositionen och korrelerades sedan med biologiska aktiviteten och Es,min värdena. Om en statistiskt signifikant korrelation observerades mellan aktiveringsenergin och Es,min värdena, hade detta varit en indikation att Es,min värden kan användas för att ersätta aktiveringsenergin. Es,min värden har en jämförelsevis låg beräkningskostnad. Dock observerades ingen statistiskt signifikant korrelation mellan Es,min värdena och biologiska aktiviteten. Vidare observerades ingen statistiskt signifikant korrelation mellan aktiveringsenergin och biologiska aktiviteten och/eller Es,min värdena. Därmed fanns flera indikationer att den tänkta reaktionsmekanismen var felaktig. Under efterforskningen hittades en studie som visade att en-elektronreduktionsmekanismen var den mest troliga reaktionsmekanismen för den undersökta reaktionen. Detta kan vara en förklaring till varför en statistiskt signifikant korrelation kunde observeras mellan LUMO och biologiska aktiviteten, medan ingen korrelation observerades för Es,min, Vs,max och aktiveringsenergin mot biologiska aktiviteten. Avsaknaden av en korrelation för dessa parametrar anses bero på att den föreslagna reaktionsmekanismen var felaktig. Vidare studier hade behövts för att undersöka dessa parametrars förmåga att kunna förutse mutagenicitet. / Mutagenicity of various compounds is traditionally predicted by conventional in vivo and in vitro methods. However, transitioning to in silico methods would be beneficial both ethically and environmentally. The descriptors that can be used to predict mutagenicity are the lowest unoccupied molecular orbital (LUMO) energy, activation energy, the local minimum / maximum electrostatic potential energy (Vs,min/Vs,max), the minimum local electron attachment energy (Es,min), etc. The activation energy is a descriptor that can predict mutagenicity accurately provided that the reaction mechanism is known or can be assumed. However, determining the activation energy is computationally costly. Mutagen-X (MX) and its analogues (compounds with the same backbone but different functional groups, 29 compounds in total), are compounds of which the mutagenicity had been characterized by traditional means but recently also using an in silico method – molecular modeling. Molecular modeling had been successively employed in the study by Kari Tuppurainen [Source]; the LUMO of MX and its analogues had been computed and, importantly, the obtained values demonstrated a statistically significant correlation with the biological activity determined using Ames test. The aim of this thesis was to investigate whether the mutagenicity of MX and its analogues could also be determined by computing Es,min, Vs,max and the activation energy. The studied reaction was a Michael addition reaction between an amine group on the guanine nucleobase and the beta position of MX and its analogues. Therefore, the studied parameters (Es,min, Vs,max and the activation energy) were evaluated at the beta position. The computed Es,min values were correlated with the biological activity. Activation energies for MX and its analogues were also computed at the beta position and then correlated with the biological activity and Es,min values.  If a highly statistically significant correlation between the activation energy and Es,min values at the beta position would have been observed, that would indicate that Es,min values  could be used as a substitute for the activation energy. Es,min values have comparatively low computational cost. However, no statistically significant correlation between Es,min values and the biological activity was observed. Furthermore, no statistically significant correlation was observed between the activation energy and biological activity and/or Es,min values, respectively. Thus, there were several indications that the proposed reaction mechanism was incorrect. After consulting literature, we learned that the one electron reduction mechanism would be a more probable reaction mechanism. This could be an explanation as to why a highly statistically significant correlation could be observed for LUMO vs. the biological activity, whereas no correlation was observed for Es,min, Vs,max, the activation energy versus the biological activity. The absence of a correlation for these parameters is thought to be due to the proposed reaction mechanism being inaccurate. Additional studies would have to be performed to further investigate the predictive abilities for mutagenicity of the studied parameters.

Hohe Partikelemissionen und starke mutagene Wirkungen wurden nach der Verbrennung von Pflanzenöl in Dieselmotoren beobachtet. Diese Studie untersuchte die Hypothese, dass diese Ergebnisse durch die Menge der ungesättigten oder mehrfach ungesättigten Fettsäuren aus pflanzlichen Ölen beeinflusst werden und dass Mischungen aus Dieselkraftstoff und Pflanzenöl mutagen sind. Drei verschiedene Pflanzenöle (Leinöl, LÖ; Palmöl, PÖ; Rapsöl, RÖ), Mischungen von 20% Pflanzenöl und 80% Dieselkraftstoff (B20) und 50% Pflanzenöl und 50% Dieselkraftstoff (B50) sowie herkömmlicher Dieselkraftstoff (DK) wurden in einem Dieselmotoren verbrannt. Die Abgase wurde auf partikuläre Emissionen und die mutagene Wirkung im Vergleich zu Emissionen von DK untersucht. Der Motor wurde im European Stationary Cycle betrieben. Die Partikelmasse wurde gravimetrisch gemessen während die Mutagenität unter Verwendung des bakteriellen Rückmutationsversuchs mit Tester Stämmen TA98 und TA100 bestimmt wurde. Bei der Verbrennung von LÖ entstand die größte Partikelmasse (PM). Im Vergleich zu DK war die lösliche organische Fraktion (LOF) besonders hoch. RO präsentiert die zweithöchste PM und LOF, gefolgt von PÖ, die kaum über DK lag. B50 zeigte die niedrigste Menge an PM während B20 so hoch lag wie DK. RÖ zeigte die höchste Anzahl an Mutationen der Pflanzenöle gefolgt von LÖ. PÖ war weniger mutagen, aber immer noch stärker als DK. B50 zeigte ein höheres mutagenes Potential als B20. Während PM und LOF stark mit dem Gehalt an mehrfach ungesättigten Fettsäuren in den Pflanzenölen korrelierten hatte die Mutagenität eine signifikante Korrelation mit der Menge der gesamten vorhandenen ungesättigten Fettsäuren. Pflanzenölblends scheinen weniger mutagen als die reinen Öle zu sein und das mutagene Maximum im Vergleich zu Blends mit Biodiesel und DK verschobenen. Diese Studie unterstützt die Hypothese, dass die Zahl der Doppelbindungen in ungesättigten Fettsäuren von Pflanzenölen Bei Verbrennung in Dieselmotoren die Menge der emittierten Partikel und die Mutagenität des Abgases beeinflussen. Das Maximum der Mutagenität verschiebt sich bei Pflanzenölblends im Vergleich zu Biodieselblends. Weitere Untersuchungen müssen die kausalen Zusammenhang aufzuklären und wo das Maximum der Pflanzenölblends liegt.

Orientador: Eliana Aparecida Varanda / Banca: Eliana Aparecida Varanda / Banca: Marcelo Aparecido da Silva / Banca: Luís Vitor Silva do Sacramento / Resumo: A família Eriocaulaceae possui cerca de 1200 espécies divididas em 10 gêneros e suas espécies de plantas são conhecidas como sempre-vivas, por sua grande durabilidade e coloração paleácea. Neste trabalho foram estudadas as espécies: Eriocaulon ligulatum, Leiothrix flavescens e Leiothrix spiralis, as quais foram avaliadas quanto à mutagenicidade e estrogenicidade e algumas substâncias isoladas foram utilizadas para um estudo de relação estrutura-atividade mutagênica e estrogênica. Para avaliação da mutagenicidade, utilizou-se o teste de Ames, e o teste RYA (Recombinant Yeast Assay) foi o empregado para avaliação da estrogenicidade. Os resultados da atividade mutagênica demonstraram que apenas E. ligulatum foi considerado mutagênico e isso foi atribuído às isocumarinas e flavonóides agliconas. Os estudos de relação estrutura-atividade mutagênica mostraram que esta ação foi devida à presença de hidroxilas em posições estratégicas e à ausência de glicosilações, metoxilações, ou qualquer outro tipo de substituição. Para complementar os estudos de relação estrutura-atividade mutagênica com as isocumarinas, utilizou-se resultados já publicados de mutagenicidade de moléculas semelhantes à isocumarina eriocaulina, isolada de E. ligulatum. Verificou-se que os dímeros de isocumarinas têm a sua mutagenicidade influenciada pela conformação espacial, pela presença de grupos hidroxilas mais afastados de grupos volumosos, e pelo tipo de ligação que une os seus monômeros. Quando o potencial estrogênico foi avaliado, apenas a L. flavescens apresentou resultados positivos e que esses são devidos à presença de flavonas agliconas, como a luteolina e a metoxiluteolina. As mesmas isocumarinas, pertencentes a outras espécies da família Eriocaulaceae, avaliadas no teste de Ames, foram avaliadas no teste RYA... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Eriocaulaceae family comprises around 1200 species, divided into 10 genera, and their plant species are known as "sempre-vivas" (everlasting flowers) for its durability and color. In this work the species Eriocaulon ligulatum, Leiothrix flavescens and Leiothrix spiralis were studied. These species were evaluated for the mutagenic and the estrogenic potential and some of their isolated compounds were used for a study of structuremutagenic and estrogenic activities. To assess mutagenicity we used Ames test and the Recombinant Yeast Assay (RYA test) was used for evaluation of estrogenicity. The results of mutagenic activity showed that only E. ligulatum presented mutagenicity and that these results were due to its naphthopyranones and flavonoid aglicons. The structuremutagenic activity studies shown that this action were due to the presence of hydroxyl groups in strategic positions and no glycosylations, methoxylation or any type of substitutions. To complement the studies of structure-mutagenic activity with the naphthopyranones, we use results already published of the mutagenicity of similar compounds to the naphthopyranone eriocaulina, isolated from E. ligulatum, and compare them with the data from ericauline. It was found that the dimers of naphthopyranones have their mutagenicity influenced by its spatial conformation, for the presence of hydroxyl groups furthest away from large groups, and the type of connection that join their monomers. When the estrogenic potential was assessed, we found that only L. flavescens showed positive results and that these results are due to the presence of flavones in the form of aglycones, such as luteolin and methoxyluteolin. The same naphthopyranones belonging to other species of Eriocaulaceae family, evaluated in the Ames test, were assessed in the RYA test. Their results were crucial for the establishment of structureestrogenic activity... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:30:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-10-04Bitstream added on 2014-06-13T21:01:12Z : No. of bitstreams: 1 varella_sd_dr_arafcf.pdf: 406128 bytes, checksum: 731423647cfb057752f7d36b74cee720 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / A exposição ocupacional a solventes orgânicos é um sério problema para milhares de trabalhadores. A literatura demonstra a ocorrência de um elevado risco de danos no material genético desses indivíduos, no entanto, os efeitos da mistura dos solventes orgânicos não são bem conhecidos. As diferenças genéticas (polimorfismos enzimáticos) também têm um importante papel na capacidade de ativação e de detoxificação de xenobióticos, incluindo os solventes orgânicos. As mutações causadas por agentes ambientais associadas aos diferentes genótipos, são fatores relacionados ao desenvolvimento de neoplasias e outras doenças degenerativas. O ensaio de mutagenicidade urinária indica a ocorrência de possíveis lesões préclínicas enquanto que a determinação dos polimorfismos enzimáticos mostra um perfil genético de risco. Assim, os profissionais da saúde envolvidos com a qualidade de vida do trabalhador, podem ter subsídios para o controle da exposição ocupacional e conseqüentemente evitar o aparecimento de doença (lesão clínica), principalmente o câncer. O trabalho diário num laboratório de pesquisa onde são utilizados vários tipos de solventes é igualmente preocupante. Diante disso, este estudo teve os seguintes objetivos: caracterizar a atividade mutagênica na urina de 30 indivíduos ocupacionalmente expostos a solventes orgânicos e indivíduos sem essa exposição (controles); identificar o polimorfismo constitucional desses indivíduos para os genes GSTM1, GSTT1 e CYP2E1 ; e tentar correlacionar a influência desses genótipos com a atividade mutagênica urinária. A coleta da urina foi realizada em frascos de polietileno durante o dia de trabalho, até a obtenção de aproximadamente 1000mL. Para a concentração e extração dos compostos presentes na urina foi usada a resina XAD-2 e o solvente acetona. Diferentes concentrações... / The occupational exposure to organic solvents is a serious problem to millions of workers. The reports shows a high risk of genetic damage on these workers. However, the effects of mixtures of solvents are not well known. The genetic differences (enzimatic polymorphisms) are very important for the capacity of activating and detoxifying carcinogens, such as organic solvents. Mutations caused by environmental agents associated with the different genotypes are related to cancer development and other degenerative diseases. The urinary mutagenicity assay shows pre-clinical damages while the enzimatic polymorphisms show a genetic risk profile. In this way, the health professionals can have subsity to occupational exposure control in order to avoid disease development (clinical damage), cancer especially. The work in a research laboratory that uses several types of solvents is equaly preocupating. In this way, in this study the genotyping approach was used to study the influence of the metabolic polymorphisms CYP2E1, GSTM1 and GSTT1 on urinary mutagenicity, detected with Salmonella/microsome assay, in 30 subjects exposed to solvents, and 30 subjects without occupational exposure (controls). Urine samples were collected in polyethylene containers at the end of the work shift. For the concentration and extraction of urine samples was used the XAD-2 resin and acetone as eluting agent. Different doses of extract (1.5; 3.0; 6.0 and 12.0 mL equivalents per plate) were tested on Salmonella typhimurium strains TA100 and YG1024, with and without metabolic activation. Genomic DNA was extracted from blood and the GSTM1, GSTT1 and CYP2E1-PstI genotypes were deternined using a PCR method. The mutagenic activity of urine samples from exposed workers shows a significant difference (p£ 0.05) when compared to those in the control group in the Salmonella typhimurium YG1024 with S9 mix... (Complete abstract, click electronic access below)