RESUMEN
The effect of the antibiotic novobiocin on human recombinant tumor necrosis factor (TNF)-induced sister-chromatid exchanges (SCEs) were examined in human peripheral blood lymphocytes. TNF, when introduced in a dose range of 10-1000 U/ml at the initiation of culture, was found to cause a significant increase in SCE frequency. The simultaneous addition of TNF and novobiocin (25 micrograms/ml) in the assay resulted in no increase of SCE frequency. Delayed (for 24 h) addition of novobiocin suppressed the induction of SCEs by 50, 100 and 500 U/ml but not by 1000 U/ml of TNF.
Asunto(s)
Novobiocina/farmacología , Intercambio de Cromátides Hermanas/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Células Cultivadas , Femenino , Humanos , Linfocitos/efectos de los fármacos , Proteínas Recombinantes/farmacología , Inhibidores de Topoisomerasa IIRESUMEN
Cytogenetic analysis of chromosomal aberrations (CA) in 175,229 cells from 1113 individuals, both unexposed and occupationally or environmentally exposed to heavy metals (mercury and lead), organic (styrene, formaldehyde, phenol and benzo(a)pyrene) and inorganic (sulfur and nitrogen oxides, hydrogen and ammonium fluorides) volatile substances and/or ionizing radiation was performed. In addition, 11,250 cells from 225 individuals were scored for the frequency of sister-chromatid exchanges (SCE). Increased frequencies of CA were found in all occupationally exposed groups. A principal difference between the exposure to heavy metals and organic substances was found: increase in the CA frequency was dependent on duration of exposure to mercury but not dependent on duration of exposure to styrene, formaldehyde and phenol. A higher CA incidence was found in lymphocytes of children living in the vicinity of a plant manufacturing phosphate fertilizers. This indicates that children are a sensitive study group for the assessment of environmental exposure. However, the results of SCE analysis in these children were inconclusive. Exposure to ionizing radiation was found to cause chromosome breaks and chromatid exchanges in Chernobyl clean-up workers and chromatid breaks, chromatid exchanges, dicentric chromosomes and chromosome translocations in workers from the Ignalina Nuclear Power Plant. The increased frequency of chromatid exchanges in individuals exposed to ionizing radiation was quite unexpected. This may be attributed to the action of some unrecognized life-style or occupational factors, or to be a result of radiation-induced genomic instability. Also an increased SCE frequency was found in lymphocytes of Chernobyl clean-up workers.
Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Contaminantes Radiactivos del Aire/efectos adversos , Aberraciones Cromosómicas , Cromosomas Humanos/efectos de los fármacos , Cromosomas Humanos/efectos de la radiación , Exposición Profesional/efectos adversos , Intercambio de Cromátides Hermanas , Adolescente , Adulto , Anciano , Niño , Daño del ADN , Monitoreo del Ambiente , Femenino , Humanos , Lituania , Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Masculino , Metales Pesados/efectos adversos , Persona de Mediana Edad , Reactores Nucleares , Compuestos Orgánicos/efectos adversos , Radiación Ionizante , Liberación de Radiactividad Peligrosa , UcraniaRESUMEN
Recombinant human tumor necrosis factor alpha (TNF) was found to cause a significant increase in cell proliferation rates and sister chromatid exchange (SCE) frequency in phytohemagglutinin-stimulated human lymphocytes in vitro. The cells were treated for the entire cultivation time with 10, 50, 100, 500, 1000 and 5000 U/ml TNF. Cell proliferation rates, as measured by the replication index, increased significantly (P less than 0.01) in a concentration-independent manner. The maximal extent of SCE induction (15.18 +/- 0.57 versus 10.26 +/- 0.45 SCEs/cell in control, P less than 0.001) was observed with 50 U/ml TNF.