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Aryl hydrocarbon hydroxylase activity was studied in cultured human lymphocytes using 3-methylcholanthrene, 1,2- benzanthracene, and 4'-bromoflavone as inducers. The substrates used to run the 60 minute assay were benzo(α)pyrene and diphenyloxazole. At the optimum bromoflavone concentration for induction of aryl hydrocarbon hydroxylase, the induced enzymatic activity compared favorably with that of aryl hydrocarbon hydroxylase induced by 3MC in a 96 hour lymphocyte culture using BP as the assay substrate. The whole cell human lymphocyte system was found to have as much or more activity in 20 ml vials using Joklik's-Modified Minimum Essential Medium at a pH optimum of 7.5 with no co-factor added as did the Roswell Park assay system. The whole cell assay showed that levels of aryl hydrocarbonhydroxylase inducibility in lumphocytes from smokers and non-smokers varied without regard to the subjects' smoking habits. The assay system also indicated that intact lymphocytes generate a similar group of benzo(α)pyrene metabolites as that produced by a hepatic microsomal preparation from C57B1/6J mice.

Traditional liquid coolants used in metal machining are known to contain chemical carcinogens that could present serious health risks for machine operators and have inherent waste disposal concerns on the environment. In lessening these adverse effects, the manufacturing industry continually seeks to develop machining techniques incorporating liquid-less (dry) methods or environmentally benign coolants. Air-jet cooling is widely regarded as a viable alternative for liquid coolants in machining processes. This thesis proposes a novel air jet cooling arrangement, and assesses its thermal effectiveness and operational compatibility for specific requirements in metal cutting operation. For tests, steel rods were machined on a standard lathe workbench at selected cutting depth, feed and speed. Type 1040 steel, which is commonly used in automobile industry, was chosen as work piece material. Instead of traditional liquid coolant, a specially designed compressed air jet is used to dissipate heat generation in the cutting zone at the tool tip. The tool tip is presented orthogonally to the work piece to maintain conformity with relevant established cutting tool theories. A special air jet configuration based on a Ranque-Hilsch vortex tube was designed and developed for cooling the cutting zone and tool tip. The tool tip temperatures were measured by installing thermocouples at strategic locations on the tool piece and recorded on a data-logger for a range of cutting depths, feeds and speeds. The cutting power was measured with a power meter attached to the electrical power supply to the lathe. For comparison purposes, tests were also conducted with conventional single-nozzle air jets in place of the vortex-tube jets, using traditional liquid coolant and without any cooling applied to the tool tip. / A thermal vision camera was also deployed for selected tests to ascertain the temperature characteristics at the tool tip. The data was analysed to establish the thermal characteristics at the tool tip with vortex tube air jet, conventional air jet and no air jet cooling. The measured temperatures and cutting data were used to make assessments on cooling efficiency of jets used and surface finish quality of work piece. Estimates of tool life were made from the cutting theory to determine the effectiveness of the cooling systems used in the machining process. It is found that the proposed vortex tube based air jet cooling arrangement provides a highly efficient heat removal mechanism for metal cutting and delivers thermal cooling performance very much comparable to traditional liquid coolants without the inherent chemical exposure risks to machine operators and harmful impact on the environment. With the proposed air jet cooling, the tool life is very much unchanged and the surface finish quality of work piece shows no significant change while savings will realise though lesser dependency on liquid coolant requiring careful disposal and associated costs.

A inflamação é um componente essencial presente no microambiente tumoral, sendo relacionada a muitos tipos de câncer, como o de pulmão e de fígado. O objetivo foi estudar a influência de fatores genéticos relacionados à inflamação no desenvolvimento do câncer através da análise da progressão tumoral em camundongos AIRmax e AIRmin, geneticamente selecionados para máxima ou mínima resposta inflamatória. Os carcinomas foram induzidos pela injeção de Uretana ou DEN. 32 semanas após dose, a maioria dos AIRmax apresentaram tumores hepáticos, enquanto AIRmin foram resistentes. O contrário aconteceu com câncer de pulmão: todos os AIRmin foram acometidos e poucos AIRmax apresentaram pequenas lesões. As proteínas de fase aguda IL-6, TNF<font face=\"Symbol\">a e IL-1<font face=\"Symbol\">b são importantes nesse processo, pois tiveram aumento de produção em órgãos alvo horas após injeção. Esses resultados sugerem que um grupo de loci gênicos controla a resposta inflamatória e a susceptibilidade/resistência a diversos tipos de câncer e ressaltam o papel específico de células locais no controle da imunidade ao tumor. / Inflammatory components are an essential part of the tumor microenvironment being crucial in some types of cancer. Our objective was to study the influence of genetic factors relevant to inflammatory response regulation on cancer development by the comparative analysis of carcinogen-induced liver and lung tumors in AIRmax and AIRmin mouse strains, genetically selected for maximum and minimum inflammatory responsiveness. The carcinomas were induced by the injection of Urethane or DEN. 32 weeks after treatment, most AIRmax had liver tumors whereas AIRmin mice were resistant. The inverse occured in lungs: all AIRmin were affected and the incidence in AIRmax was 27.3%. The acute phase proteins IL-6, TNF<font face=\"Symbol\">a and IL-1<font face=\"Symbol\">b seem to be important in this process, with increased production in target organs hours after drug injection. These results provide a demonstration that a group of genes controls the inflammatory response and susceptibility or resistance to different types of cancers and also highlight the specific role of local cells in the control of tumor immunity.

A inflamação é um componente essencial presente no microambiente tumoral, sendo relacionada a muitos tipos de câncer, como o de pulmão e de fígado. O objetivo foi estudar a influência de fatores genéticos relacionados à inflamação no desenvolvimento do câncer através da análise da progressão tumoral em camundongos AIRmax e AIRmin, geneticamente selecionados para máxima ou mínima resposta inflamatória. Os carcinomas foram induzidos pela injeção de Uretana ou DEN. 32 semanas após dose, a maioria dos AIRmax apresentaram tumores hepáticos, enquanto AIRmin foram resistentes. O contrário aconteceu com câncer de pulmão: todos os AIRmin foram acometidos e poucos AIRmax apresentaram pequenas lesões. As proteínas de fase aguda IL-6, TNF<font face=\"Symbol\">a e IL-1<font face=\"Symbol\">b são importantes nesse processo, pois tiveram aumento de produção em órgãos alvo horas após injeção. Esses resultados sugerem que um grupo de loci gênicos controla a resposta inflamatória e a susceptibilidade/resistência a diversos tipos de câncer e ressaltam o papel específico de células locais no controle da imunidade ao tumor. / Inflammatory components are an essential part of the tumor microenvironment being crucial in some types of cancer. Our objective was to study the influence of genetic factors relevant to inflammatory response regulation on cancer development by the comparative analysis of carcinogen-induced liver and lung tumors in AIRmax and AIRmin mouse strains, genetically selected for maximum and minimum inflammatory responsiveness. The carcinomas were induced by the injection of Urethane or DEN. 32 weeks after treatment, most AIRmax had liver tumors whereas AIRmin mice were resistant. The inverse occured in lungs: all AIRmin were affected and the incidence in AIRmax was 27.3%. The acute phase proteins IL-6, TNF<font face=\"Symbol\">a and IL-1<font face=\"Symbol\">b seem to be important in this process, with increased production in target organs hours after drug injection. These results provide a demonstration that a group of genes controls the inflammatory response and susceptibility or resistance to different types of cancers and also highlight the specific role of local cells in the control of tumor immunity.

Camundongos AIRmax são resistentes e AIRmin susceptíveis à carcinogênese de pele por repetidas doses de DMBA. Apenas os AIRmin desenvolvem reação de hipersensibilidade de contacto (CHS) inicial seguida de tumores de pele e pulmão. O receptor aril hidrocarboneto (AHR) é importante no metabolismo do DMBA. Após ligação ao agonista este fator de transcrição aumenta a expressão de enzimas CYP450 necessários à sua metabolização. Nos AIRmin ocorreu um aumento do mRNA de IL1<font face=\"symbol\">b, TNF<font face=\"symbol\">a, IL6, TGF<font face=\"symbol\">b1 e CYP1B1 na pele às 48h após as doses de DMBA. Nos AIRmax não houve alteração. O aumento de expressão de citocinas e de P450 em AIRmin é coerente com a indução de CHS por DMBA dependente da ativação do AHR. Todos os AIRmax são homozigotos para o alelo Ahrd que confere resistência a CHS e carcinogênese enquanto os AIRmin portam o alelo Ahrb1 que confere susceptibilidade. Esta segregação alélica sugere a participação do Ahr como marcador ou gene que regula a carcinogênese e inflamação. Esta última hipótese foi confirmada pela análise de linkage dos genótipos Ahr parentais com o grau da inflamação em população F2 (AIRmax x AIRmin). Fatores genéticos ligados ao AHR e reações imunes específicas contribuem para a diferente susceptibilidade das linhagens à carcinogênese. / AIRmax mice are resistant and AIRmin susceptible to skin carcinogenesis by repeated DMBA doses. AIRmin mice developed initial contact hypersensitivity reaction (CHS) and late skin and lung tumors. The aryl hydrocarbon receptor (AHR) plays important roles in DMBA metabolism. Upon binding to agonist this transcription factor induces the expression of CYP P450 enzymes. Up regulated levels of IL1<font face=\"symbol\">b, TNF<font face=\"symbol\">a, IL6, TGF<font face=\"symbol\">b1 and CYP1B1 mRNAs were found in the skin of AIRmin at 48h after DMBA. In AIRmax the levels were similar to controls. The cytokine and P450 mRNA up regulation in AIRmin is coherent with CHS elicitation by DMBA dependent on AHR activation. All AIRmax were found homozygous for the Ahrd allele, which confers resistance to CHS and carcinogenesis, whereas all AIRmin are homozygous for the Ahrb1 allele, related to susceptibility. The allelic segregation in the lines suggests that Ahr is a marker or a gene involved in carcinogenesis and in inflammatory response control. This last hypothesis was confirmed by linkage analysis of Ahr parental genotypes with acute inflammation degree in F2 (AIRmax x AIRmin) population. The results point to genetic and molecular factors underlying the differential susceptibility of AIRmax and AIRmin mice to carcinogenesis.

Camundongos AIRmax são resistentes e AIRmin susceptíveis à carcinogênese de pele por repetidas doses de DMBA. Apenas os AIRmin desenvolvem reação de hipersensibilidade de contacto (CHS) inicial seguida de tumores de pele e pulmão. O receptor aril hidrocarboneto (AHR) é importante no metabolismo do DMBA. Após ligação ao agonista este fator de transcrição aumenta a expressão de enzimas CYP450 necessários à sua metabolização. Nos AIRmin ocorreu um aumento do mRNA de IL1<font face=\"symbol\">b, TNF<font face=\"symbol\">a, IL6, TGF<font face=\"symbol\">b1 e CYP1B1 na pele às 48h após as doses de DMBA. Nos AIRmax não houve alteração. O aumento de expressão de citocinas e de P450 em AIRmin é coerente com a indução de CHS por DMBA dependente da ativação do AHR. Todos os AIRmax são homozigotos para o alelo Ahrd que confere resistência a CHS e carcinogênese enquanto os AIRmin portam o alelo Ahrb1 que confere susceptibilidade. Esta segregação alélica sugere a participação do Ahr como marcador ou gene que regula a carcinogênese e inflamação. Esta última hipótese foi confirmada pela análise de linkage dos genótipos Ahr parentais com o grau da inflamação em população F2 (AIRmax x AIRmin). Fatores genéticos ligados ao AHR e reações imunes específicas contribuem para a diferente susceptibilidade das linhagens à carcinogênese. / AIRmax mice are resistant and AIRmin susceptible to skin carcinogenesis by repeated DMBA doses. AIRmin mice developed initial contact hypersensitivity reaction (CHS) and late skin and lung tumors. The aryl hydrocarbon receptor (AHR) plays important roles in DMBA metabolism. Upon binding to agonist this transcription factor induces the expression of CYP P450 enzymes. Up regulated levels of IL1<font face=\"symbol\">b, TNF<font face=\"symbol\">a, IL6, TGF<font face=\"symbol\">b1 and CYP1B1 mRNAs were found in the skin of AIRmin at 48h after DMBA. In AIRmax the levels were similar to controls. The cytokine and P450 mRNA up regulation in AIRmin is coherent with CHS elicitation by DMBA dependent on AHR activation. All AIRmax were found homozygous for the Ahrd allele, which confers resistance to CHS and carcinogenesis, whereas all AIRmin are homozygous for the Ahrb1 allele, related to susceptibility. The allelic segregation in the lines suggests that Ahr is a marker or a gene involved in carcinogenesis and in inflammatory response control. This last hypothesis was confirmed by linkage analysis of Ahr parental genotypes with acute inflammation degree in F2 (AIRmax x AIRmin) population. The results point to genetic and molecular factors underlying the differential susceptibility of AIRmax and AIRmin mice to carcinogenesis.