RESUMO
Tumor cells generally display low lipid peroxidation. A low content of polyunsaturated fatty acids in membrane phospholipids is a possible cause of their decreased susceptibility to lipid peroxidation. To investigate the importance of substrate availability in eliciting lipid peroxidation and to study cell viability in conditions of stimulated lipid peroxidation, AH-130 hepatoma cells were enriched with arachidonic acid. The enriched hepatoma cells showed increased mortality correlated with the increased incorporation of arachidonic acid in membrane phospholipids. When 0.5 mM arachidonic acid was added to hepatoma cells, this fatty acid reached a percentage content similar to that found in hepatocytes. Hepatoma cells enriched with this concentration were further incubated to determine their susceptibility to lipid peroxidation; mortality increased in parallel with increased thiobarbituric acid-reactive substance production. The highest mortality was in hepatoma cells treated with ascorbate/FeSO4. Mortality in normal cells was low, although they had a high production of thiobarbituric acid-reactive substances. The high capability of normal cells to metabolize the products of lipid peroxidation might explain the different viabilities of normal cells and hepatoma cells. It may therefore be possible to modify the composition of fatty acids of hepatoma cells in order to sensitize them to the toxic effect of prooxidant agents.
Assuntos
Ácidos Araquidônicos/metabolismo , Peroxidação de Lipídeos , Neoplasias Hepáticas Experimentais/metabolismo , Lipídeos de Membrana/metabolismo , Animais , Ácido Ascórbico/farmacologia , Sobrevivência Celular , Meios de Cultura , Compostos Ferrosos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Microssomos Hepáticos/metabolismo , RatosRESUMO
The susceptibility of rat liver tissue to oxidative stress during its neoplastic transformation was analyzed by both qualitative and quantitative measurements of the carbonyl products of lipid peroxidation. Diethylnitrosamine was used as initiating agent of hepatocarcinogenesis and lipid peroxidation levels were monitored in the homogenates from normal liver, hyperplastic nodules and tumour, incubated in the presence or in the absence of ascorbate or adenosine diphosphate-iron complex. While the basal levels of lipid peroxidation in the three experimental conditions were found to be quite similar, in the presence of the pro-oxidant stimulus a remarkable reduction in aldehyde production was shown not only by the hepatoma tissue but also by the preneoplastic nodules.
Assuntos
Transformação Celular Neoplásica , Peróxidos Lipídicos/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Aldeídos/metabolismo , Animais , Ácido Araquidônico , Ácidos Araquidônicos/análise , Cromatografia Líquida de Alta Pressão , Dietilnitrosamina , Ácidos Graxos/análise , Hiperplasia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Malondialdeído/metabolismo , Oxirredução , Fosfatidiletanolaminas/análise , Ratos , Ratos EndogâmicosRESUMO
Outer and inner membranes isolated from hepatoma AH-130 and rat liver mitochondria were used to study phospholipid composition. The phosphatidylethanolamine content increased and that of phosphatidylcholine decreased in ;whole mitochondria and isolated membranes. The ratio between the 2 phospholipids increased 47% and 117% in the inner and outer membranes respectively. A small decrease of diphosphatidylglycerol also occurred in the hepatoma mitochondria inner membrane. In contrast to the results of previous work, no sphingomyelin was found in hepatoma mitochondria and isolated membranes.
Assuntos
Membranas Intracelulares/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Mitocôndrias Hepáticas/metabolismo , Fosfolipídeos/análise , Animais , Cardiolipinas/análise , Neoplasias Hepáticas Experimentais/ultraestrutura , Mitocôndrias Hepáticas/ultraestrutura , Fosfatidilcolinas/análise , Fosfatidiletanolaminas/análise , Fosfatidilinositóis/análise , Ratos , Esfingomielinas/análiseRESUMO
In some chemically-induced hepatomas and in cultured transformed cells the aldehyde dehydrogenase activity was found increased in the presence of aromatic aldehyde as substrate. We studied this enzyme during diethyl-nitrosamine carcinogenesis in rat liver by using an aliphatic aldehyde, 4-hydroxynonenal, as substrate. 4-Hydroxynonenal is an important product of lipid peroxidation. The NAD- and NADP-dependent aldehyde dehydrogenase of the cytosolic fraction and the NADP-dependent aldehyde dehydrogenase of the microsomes show higher values in nodules and hepatoma than in normal liver. These results suggest that increased aldehyde dehydrogenase, when 4-hydroxynonenal is used, can be considered a marker of the neoplastic process, in the same way as the level of aldehyde dehydrogenase increased in presence of aromatic aldehyde.
Assuntos
Aldeído Desidrogenase/metabolismo , Aldeídos/metabolismo , Dietilnitrosamina , Neoplasias Hepáticas Experimentais/enzimologia , Fígado/enzimologia , Lesões Pré-Cancerosas/enzimologia , Animais , Peróxidos Lipídicos/biossíntese , Fígado/ultraestrutura , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/ultraestrutura , Masculino , NAD/metabolismo , NADP/metabolismo , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/ultraestrutura , Ratos , Ratos Endogâmicos F344RESUMO
Several enzymes metabolize the toxic aldehydes produced during lipid peroxidation, such as 4-hydroxynonenal. During carcinogenesis induced by diethylnitrosamine in rat liver, an increase in aldehyde dehydrogenase, in comparison with normal liver, has already been shown. This paper demonstrates that, although to a lesser extent than aldehyde dehydrogenase, aldehyde reductase and glutathione-S-transferase also increase during carcinogenesis. Of the latter two enzymes, aldehyde reductase increases more markedly in a progressive fashion during the months of development of nodules and hepatoma. The increase of enzymes able to metabolize 4-hydroxynonenal, as well as other aldehydes, is certainly important in protecting tumour cells against cytotoxic effect of aldehydes.
Assuntos
Álcool Desidrogenase/metabolismo , Aldeído Redutase/metabolismo , Glutationa Transferase/metabolismo , Neoplasias Hepáticas Experimentais/enzimologia , Animais , Fígado/enzimologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Masculino , Ratos , Ratos Endogâmicos F344RESUMO
Biliary epithelial cells (BEC) and parenchymal cells isolated from normal rat liver were exposed in vitro to a number of toxic compounds. BEC were found to be highly sensitive to concentrations of menadione (100 microM) and cumene hydroperoxide (10 microM) that are usually not effective as toxic agents in hepatocytes under normoxic conditions. On the other hand, BEC were not affected by concentrations of carbon tetrachloride or 7-ethoxycoumarin that are known to exert toxic effects on hepatocytes. The development of both menadione- and cumene hydroperoxide-induced toxic injury in BEC followed a common and time-correlated pattern, and included a strong depletion of GSH, depletion of protein thiols and an increase in the extent of cell death. The damage induced by cumene hydroperoxide was found to be independent of lipid peroxidative processes and was prevented by a pre-incubation with desferrioxamine. The cytotoxicity of menadione was further exacerbated by dicoumarol but was not prevented by desferrioxamine or promethazine. The mechanisms underlying BEC injury and death induced by the quinone and by the organic hydroperoxide are discussed in relation to the known biochemical characteristics of BEC.
Assuntos
Derivados de Benzeno/toxicidade , Fígado/efeitos dos fármacos , Vitamina K/toxicidade , Animais , Tetracloreto de Carbono/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Desferroxamina/metabolismo , Células Epiteliais , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Fígado/citologia , Fígado/metabolismo , Masculino , Oxirredução , Ratos , Fatores de TempoRESUMO
In vivo administration of CCl4 (2.5 ml/kg, body wt.) to rats results in an early and then progressive inhibition of the high affinity Ca2(+)-ATPase activity in rat liver plasma membranes. The derangement to the Ca2(+)-ATPase seems to be independent on a 'solvent effect' of the agent since the in vitro addition of increasing concentrations of either CCl4 or ethanol to control plasma membranes does not affect the enzymatic activity. By using the technique of vitamin E pretreatment of experimental animals we show that the damage to the Ca2(+)-ATPase seems to follow a two-step kinetics. The early inhibition of the enzyme is not prevented by alpha-tocopherol supplementation and seems then unrelated to lipid peroxidative processes. The same procedure is however able to affort a significant protection against the exacerbation of the damage to the Ca2(+)-ATPase becoming evident late during the course of CCl4 intoxication. The high affinity Ca2(+)-ATPase is affected in vitro by 4-hydroxy-nonenal (HNE), a major end-product of lipid peroxidation interacting with -SH groups. Similar results were obtained after the addition to the incubation medium of sulphydryl reagents. The possible mechanisms involved in Ca2(+)-ATPase inhibition are discussed in relation to the development of CCl4 toxicity and to the role of lipid peroxidative processes.
Assuntos
ATPases Transportadoras de Cálcio/antagonistas & inibidores , Tetracloreto de Carbono/toxicidade , Fígado/enzimologia , 5'-Nucleotidase/antagonistas & inibidores , Aldeídos/farmacologia , Animais , Tetracloreto de Carbono/farmacologia , Membrana Celular/enzimologia , Dinitroclorobenzeno/farmacologia , Etilmaleimida/farmacologia , Cinética , Peroxidação de Lipídeos , Masculino , Ratos , Ratos Endogâmicos , Vitamina ERESUMO
The purpose of this study was to compare the pattern of mortality of blue-collar workers employed less and more than 1 year in the man-made vitreous fiber (MMVF) and the reinforced plastic industries, the latter group being exposed to styrene. We conducted an analysis among 21,784 workers with less than 1 year of employment (short-term workers) and 19,117 workers with 1 or more years of employment (long-term workers) employed in eight European countries. We conducted analyses based on external as well as internal comparisons. In both cohorts, the standardized mortality ratio for all causes among short-term workers was approximately 40% higher, compared with that for longer-term workers. In internal comparisons, the difference was reduced to 9% in the MMVF cohort and 11% in the styrene cohort. Workers with less than 1 month of employment displayed an increased mortality in both cohorts and in most countries. The increased mortality among short-term workers was not concentrated shortly after they quit employment. In both cohorts, short-term workers had a higher mortality from external causes, while little difference was seen in mortality from ischemic heart disease and malignant neoplasms. Although extra-occupational factors may contribute to increase the mortality of short-term workers and, in particular, of those employed for less than 1 month, the difference observed in analyses adjusted for characteristics of employment suggested a relatively small difference in mortality from most causes.
Assuntos
Indústria Química , Fibras Minerais , Doenças Profissionais/mortalidade , Plásticos , Adulto , Causas de Morte , Estudos de Coortes , Europa (Continente)/epidemiologia , Humanos , Masculino , Exposição Ocupacional , Estireno , Fatores de TempoRESUMO
OBJECTIVES: The goal of this study was to determine whether exposure to styrene is associated with an increased risk for neoplasms of the lymphatic and hematopoietic tissues. METHODS: A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. It involved 40,688 workers ever employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories and environmental and biological monitoring data. Cause-specific national death rates were used as the reference. Poisson regression was applied for internal comparisons. RESULTS: Among the exposed workers, no excess was observed for mortality from all neoplasms. Mortality from neoplasms of the lymphatic and hematopoietic tissues increased with time since first exposure and average level of exposure to styrene, but was not consistently associated with duration of exposure or with cumulative exposure. CONCLUSIONS: These findings leave open the possibility of an excess risk of neoplasms of the lymphatic and hematopoietic tissues among workers exposed to styrene.
Assuntos
Neoplasias/induzido quimicamente , Neoplasias/mortalidade , Exposição Ocupacional/efeitos adversos , Estirenos/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Leucemia/induzido quimicamente , Leucemia/mortalidade , Linfoma/induzido quimicamente , Linfoma/mortalidade , Masculino , Fatores de Risco , Estatística como Assunto , EstirenoRESUMO
OBJECTIVES: A historical cohort study was carried out to investigate mortality from nonmalignant diseases of the genitourinary system among workers in the reinforced plastics industry, where high workroom concentrations of styrene are encountered. METHODS: The external comparisons in this report were based on an average of 12.6 years of retrospective follow-up of 35 443 workers who were first employed in the reinforced plastics industry during 1945-1991 and were known to have been exposed to styrene in their work. For the internal comparisons, 2641 subjects with incomplete occupational histories were excluded, leaving 32 802 subjects. Previous individual exposure histories to styrene were reconstructed through job histories and environmental and biological monitoring data. RESULTS: Mortality from nonmalignant diseases of the genitourinary system (N = 20) was associated with average exposure to styrene (P for trend 0.05). Weaker increasing trends in risk were seen for time since first exposure and cumulative exposure, while no increase was identified for duration of exposure. There was a significant increasing trend in mortality from nephritis and nephrosis (N = 5), associated with an increasing average level of exposure to styrene (P for trend 0.03). No clear trend was observed for time since first exposure, duration of exposure, or cumulative exposure. CONCLUSIONS: In this large cohort study of workers exposed to styrene, mortality from nonmalignant diseases of the genitourinary system increased as the average intensity of exposure increased. This finding indicates that other data should be scrutinized.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Doenças Urogenitais Femininas/mortalidade , Doenças Urogenitais Masculinas , Doenças Profissionais , Doenças Profissionais/mortalidade , Estirenos/efeitos adversos , Poluentes Ocupacionais do Ar/análise , Monitoramento Ambiental , Monitoramento Epidemiológico , Europa (Continente)/epidemiologia , Feminino , Doenças Urogenitais Femininas/induzido quimicamente , Seguimentos , Humanos , Indústrias , Masculino , Doenças Profissionais/induzido quimicamente , Plásticos , Estudos Retrospectivos , Fatores de Risco , Estireno , Estirenos/análiseRESUMO
An increase in lipid peroxidation has been found in liver after poisoning with hepatotoxic substances and following dietary changes, i.e. choline-devoid diet and orotic acid-rich diet. In this study we analysed in the rat a model of fatty liver induced by administration of caffeine. The results seem to indicate an increased peroxidability in the liver of caffeine-treated animals, due to an increase in triglyceride content. A decrease of vitamin E which also occurs might contribute to the lipid peroxidation.
Assuntos
Fígado Gorduroso/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Animais , Cafeína , Fígado Gorduroso/induzido quimicamente , Masculino , Ratos , Ratos Endogâmicos F344 , Triglicerídeos/metabolismo , Vitamina E/metabolismoRESUMO
On two occasions in the past, Italy has been in a leading position regarding occupational health: in 1700, thanks to work carried out by Dr. B. Ramazzini, and at the beginning of this century, with the founding of the first "Clinica del Lavoro" in Milan. Experience with and considerations of the interaction between the workplace, society as a whole, and the various institutions in the field of occupational health have played an important role in the general political discussion since the 1960s. In this article, we describe the effects of the workers' model of inquiry into health hazards on work organization, the National Health Service, workers' health conditions, and the scientific milieu. We also provide an analysis of present conditions and difficulties, particularly with regard to environmental problems and perspectives.
Assuntos
Política de Saúde/tendências , Doenças Profissionais , Acidentes de Trabalho , Meio Ambiente , Feminino , História do Século XVIII , História do Século XX , Humanos , Itália , Sindicatos , Masculino , Programas Nacionais de Saúde , Doenças Profissionais/epidemiologia , Doenças Profissionais/história , Serviços de Saúde do Trabalhador/história , Mulheres TrabalhadorasRESUMO
Experience with and reflections on the interaction among the workplace, the society, and various institutions in the area of occupational health have played an important role in the general political debate in Italy since the 1960s. This paper describes the emergence of the worker's model of investigation into health hazards, an element unique to the Italian experience, and analyzes its impact on the organization of work, government policies, health institutions, and scientific research.
Assuntos
Prevenção de Acidentes , Sindicatos/história , Medicina do Trabalho/tendências , Política Pública , Segurança , História do Século XX , Humanos , Itália , Modelos Teóricos , Medicina do Trabalho/história , PolíticaRESUMO
The industrialized countries have been producing, every year from 1929, thousands of tons of polychlorinated biphenyls (PCB). Although it was known from that period the toxic activity of PCB (chlorancne), only from 1966 their presence and persistence in the environment has been detected and their mechanism of bioconcentration studied. Systematic researches to evaluate the mechanism of their toxicity, expecially for long period, have been carried out. The Italian environmental contamination of PCB is quite well defined, but only recently in Italy we have been specifically studying the industrial environment and the professionally exposed workers, to evaluate the exposure levels of PCB, the long term health effects and the possible preventive measures. In particular we are carrying out a research program in a transformer plant in the Roma area in which PCB are used as dielectrics. The methodological approach and the initial results are described.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Doenças Profissionais/induzido quimicamente , Bifenilos Policlorados/efeitos adversos , Tosse/induzido quimicamente , Exposição Ambiental , Feminino , Cefaleia/induzido quimicamente , Humanos , Masculino , Concentração Máxima Permitida , Distúrbios Menstruais/induzido quimicamente , Gravidez , Complicações na Gravidez/induzido quimicamenteRESUMO
The risk communication processes concerning atmospheric pollution and health effects in Modena, Reggio Emilia and Bologna, are described from the public health service point of view. The description includes the chronological developments, the principal events which influenced, or have been influenced by these risk communication processes, their most significant and critical aspects. Finally the air quality evaluation and its impact on risk communication is discussed.