RESUMEN
Human cirrhosis is considered an important factor in hepatocarcinogenesis. The lack of substantial genetics and cytogenetics data in human cirrhosis led us to investigate spontaneous micronuclei formation, as an indicator of chromosomal damage. The analysis was performed in hepatocytes of regenerative, macroregenerative, and tumoral nodules from 30 cases of cirrhosis (paraffin-embedded archival material), retrospectively selected: cryptogenic, hepatitis C virus, and hepatitis C virus associated with hepatocellular carcinoma (HCC). Thirteen control liver samples of healthy organ donors were included. Micronucleated hepatocytes were analyzed with Feulgen-fast-green dyeing techniques. The spontaneous frequency of micronucleated hepatocytes in both regenerative and macroregenerative nodules of all cirrhotic patients was significantly higher than for the normal control group. There was no significant difference in frequency of micronucleated hepatocytes in regenerative nodules compared with macroregenerative nodules for all cases analyzed, whereas a significantly higher frequency of micronucleated hepatocytes was detected in tumoral nodules, compared with cirrhotic regenerative nodules and normal parenchyma. A higher frequency of the nuclear anomalies termed broken-eggs was observed in hepatitis C virus-related samples. Chromatinic losses and genotoxicity already existed in the cirrhotic regenerative nodules, which might predispose to development of HCC.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Núcleo Celular/metabolismo , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Regeneración Hepática , Micronúcleos con Defecto Cromosómico/metabolismo , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Hepatitis C/patología , Hepatitis C/virología , Hepatocitos/metabolismo , Hepatocitos/patología , Hepatocitos/virología , Humanos , Hígado/patología , Hígado/virología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Pruebas de Mutagenicidad , Adhesión en Parafina , Lesiones Precancerosas/complicaciones , Lesiones Precancerosas/patología , Lesiones Precancerosas/virología , Estudios RetrospectivosRESUMEN
BACKGROUND: For topically applied drugs such as 5-fluorouracil (5-FU), dosage is not as precise as for other drug administration pathways. Consequently, quantity of drug delivered may differ among individuals and applications. 5-FU is used in treatment of different diseases and has been reported as a clastogenic compound by micronucleus assay. METHODS: To determine whether 5-FU cream (5% 5-FU) absorbed through skin can produce genotoxic or cytotoxic effect in mouse bone marrow, induction of micronucleated erythrocytes (MNE) in mouse peripheral blood was examined after cutaneous application of 5-FU daily for 5 days. RESULTS: 5-FU cream induced significant micronuclei at doses of 37.5 mg (total weight of cream)/2 cm(2) and 75.0 mg/2 cm(2), as well as cytotoxic effects at doses of 150.0 and 300.0 mg/2 cm(2). CONCLUSIONS: Cutaneous application of 5-FU increased number of MNE in mouse peripheral blood. These data emphasize the importance of using correct dose when applying drugs topically.
Asunto(s)
Eritrocitos/metabolismo , Fluorouracilo/farmacología , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Micronúcleos con Defecto Cromosómico/metabolismo , Administración Cutánea , Animales , Antimetabolitos Antineoplásicos/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Pruebas de Micronúcleos , Factores de TiempoRESUMEN
Biomass growth, micronucleus induction, and antioxidative stress enzymes (superoxide dismutase, peroxidase, glutathione reductase, and catalase) were investigated simultaneously in the Vicia faba plant exposed to cadmium in solution. The biomass lowest-observed-effect concentration (LOEC) value was 2,000 microM Cd2+. In the shoots, enzymic activities increased without concentration-response relationships. In the roots, after an initial increase, activities of all enzymes showed negative concentration-response relationships. A significant increase in micronucleus induction was observed at 20 microM Cd2+. Regarding sensitivity, our results showed that biomass endpoint was less sensitive than micronucleus induction, which was less sensitive than antioxidative enzyme activities. The increase of antioxidant stress enzyme activities in response to cadmium exposure may be taken as evidence for an enhanced detoxification capacity of V. faba plants toward reactive oxygen species (and derivatives) that might be generated in the stressed plants. Concomitant micronucleus induction may be also interpreted as a consequence of oxidative stress, upholding the view that cadmium-induced DNA damage is, to some extent, via generation of reactive (intermediate) oxygen species.
Asunto(s)
Cadmio/farmacocinética , Contaminantes Ambientales/farmacocinética , Micronúcleos con Defecto Cromosómico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Vicia faba/metabolismo , Biomasa , Cadmio/toxicidad , Catalasa/metabolismo , Contaminantes Ambientales/toxicidad , Glutatión Reductasa/metabolismo , Inactivación Metabólica , Pruebas de Micronúcleos , Peroxidasa/metabolismo , Raíces de Plantas/enzimología , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Brotes de la Planta/enzimología , Brotes de la Planta/crecimiento & desarrollo , Brotes de la Planta/metabolismo , Soluciones , Superóxido Dismutasa/metabolismo , Vicia faba/enzimología , Vicia faba/crecimiento & desarrolloRESUMEN
In the present study, we report the results of an investigation on pyrrolizidine alkaloids extracted from Senecio brasiliensis (Sprengel) Less., which were stored for more than 23 years under variable conditions of temperature and humidity and exposed to light. Both the crude alkaloid (integerrimine+retrorsine+impurities) and pure integerrimine conserved the ability to induce acute toxicity in mice, leading to the death of the animals in less than 24h. The alkaloids also conserved the potential to induce significant increases in micronucleus frequencies in polychromatic erythrocytes of mouse bone marrow compared to the negative control. The administration of alkaloids to lymphocyte cultures blocked with cytochalasin-B showed no significant increase in micronucleus frequency in binucleated cells, probably due to the lack of a metabolic activation mechanism. However, an antimitotic effect was observed.
Asunto(s)
Núcleo Celular/efectos de los fármacos , Micronúcleos con Defecto Cromosómico/metabolismo , Alcaloides de Pirrolicidina/aislamiento & purificación , Alcaloides de Pirrolicidina/farmacología , Senecio/química , Adulto , Animales , Células de la Médula Ósea/efectos de los fármacos , División Celular/efectos de los fármacos , Citocalasina B/toxicidad , Eritrocitos/efectos de los fármacos , Humanos , Linfocitos/efectos de los fármacos , Masculino , Ratones , Pruebas de Micronúcleos , Mutágenos/toxicidad , Plantas TóxicasRESUMEN
Fumonisin B(1) (FB(1)), a mycotoxin produced by Fusarium moniliforme, is a contaminant of cereals with various and complex cellular effects. FB(1) induces liver cancer in rats and has been linked to esophageal cancer in South Africa and China. The mechanisms of FB(1)-induced carcinogenesis are uncertain and the information on FB(1) mutagenic properties is limited and controversial. FB(1) contamination levels in maize and wheat from Chile were found to be similar to those in other countries. FB(1) was devoid of activity in gene mutation assays with Salmonella typhimurium strains TA100, TA102 and TA98. However, i.p. injection of FB(1) induced an increased frequency of micronuclei in mouse bone marrow polychromatic erythrocytes at 25 and 100 mg/kg. We conclude that FB(1) induces in vivo genotoxicity in the absence of in vitro mutagenicity in Salmonella.
Asunto(s)
Ácidos Carboxílicos/toxicidad , Fumonisinas , Pruebas de Mutagenicidad , Micotoxinas/toxicidad , Salmonella/genética , Animales , Células de la Médula Ósea/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Micronúcleos con Defecto Cromosómico/metabolismo , Pruebas de Micronúcleos , Neoplasias/inducido químicamente , Zea mays/microbiología , Zea mays/toxicidadRESUMEN
Painters are exposed to an extensive variety of hazardous substances such as organic solvents, lead-containing pigments and residual plastic monomers. In this particular case, workers used commercially available exterior paints and occasionally gasoline or thinner as solvents. The application or removal of paints was performed without protection (masks or gloves). To determine occupational exposure risk, a monitoring study was designed. Group selection was made after a questionnaire administration, which included questions about lifestyle and medical history to exclude exposure to other potential sources of genotoxics. Smoking and drinking habits were also considered. Blood and buccal cell samples were obtained from 25 public building male painters and from a similar number of age- and gender-matched controls. Lead levels were measured in paint samples and in individuals' blood. Organic solvents and/or its metabolites were also determined in blood. Chromosomal aberrations (CA) and sister chromatid exchanges (SCE) were determined in peripheral blood lymphocyte cultures. Also, the frequency of micronuclei (MN) in buccal cells was investigated. Painters had higher lead levels in blood (p<0.05); CA and SCE in lymphocytes and MN in epithelial cells were also elevated (p<0.05). Cytogenetic damage was significantly associated with occupational exposure time but not with the levels of lead found in blood.
Asunto(s)
Aberraciones Cromosómicas/genética , Enfermedades Profesionales/genética , Pintura/efectos adversos , Intercambio de Cromátides Hermanas/genética , Adolescente , Adulto , Factores de Edad , Contaminantes Atmosféricos/efectos adversos , Consumo de Bebidas Alcohólicas , Estudios de Casos y Controles , Interpretación Estadística de Datos , Humanos , Plomo/efectos adversos , Plomo/análisis , Plomo/sangre , Linfocitos/citología , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Masculino , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Micronúcleos con Defecto Cromosómico/metabolismo , Persona de Mediana Edad , Enfermedades Profesionales/etiología , Exposición Profesional/efectos adversos , Pintura/análisis , FumarRESUMEN
The latency period (LP) and the time of effective activity (TEA) of ethylnitrosourea (ENU) and dimethylnitrosamine (DMN) were inferred by comparing their kinetics of micronucleated polychromatic erythrocytes (MN-PCE) formation with the kinetics induced by radiation. The results indicate that LP and TEA vary between ENU and DMN. For ENU, these parameters are very similar to radiation indicating a rapid distribution, reaction and elimination. DMN presents a very long LP which agrees with the requirement of mutagen activation. The kinetics of MN-PCE production caused by DMN showed two peaks; this could be due to the presence of two different metabolites, two types of lesions in DNA or two mechanisms of MN-PCE formation. These hypotheses do not exclude each other. The data presented here support the conclusion that the comparison of MN-PCE-formation kinetics induced by chemical agents with that caused by radiation permits one to estimate the LP and the TEA, and provide information on the possible mechanism of action of chemical mutagens.