RESUMEN
Chemical interaction is of major concern in the assessment of risk by regulatory agencies. In the present study, treatment of human lymphocytes with NiSO4 (1-100 microM) or UV-light (200, 1000 ergs/mm2) induced micronuclei (MN) in a dose-dependent fashion. Statistical analysis of the interaction factor (IF), showed that combined treatments of Ni(II) (1-100 microM) with UV-light (200, or 1000 ergs/mm2) interacted antagonistically for the induction of MN. Recently we reported that Ni(II) (0.5-10 microM) with UV-light (200 or 1000 ergs/mm2) or Cr(VI) or X-rays interacted antagonistically for the induction of sister chromatid exchanges (SCE), in peripheral human lymphocytes. These observations suggest that nickel present in complex mixtures may reduce the response, even in the presence of strong MN or SCE inducers, and may lead, therefore, to an underestimate of chemical exposure as assessed by these assays. Furthermore, metals affecting certain microsteps in the process of DNA replication or repair (e.g., histones, polymerases, ligases) may have similar antagonistic effects. Further studies are therefore recommended.
Asunto(s)
Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Níquel/toxicidad , Intercambio de Cromátides Hermanas/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Humanos , Pruebas de Micronúcleos , Intercambio de Cromátides Hermanas/efectos de la radiaciónRESUMEN
In this study, individual treatments of human lymphocytes with Ni(II) [0.5-25 microM], Cr(VI) [0.65-1.30 microM], UV-light or X-rays induced SCEs in a dose-dependent fashion, and combined treatments of Ni(II) with Cr(VI), UV-light or X-rays interacted antagonistically. Nickel, at environmentally relevant exposure levels, can have the effect in complex mixtures of reducing an otherwise positive SCE response and could lead to underestimating human exposures to certain classes of chemicals or radiation. Furthermore, our data indicate that antagonism may occur when human lymphocytes are exposed simultaneously to Ni(II) and Cr(VI), suggesting an explanation for epidemiological studies reporting conflicting results for cytogenetic effects in lymphocytes of workers exposed to chromium and nickel.
Asunto(s)
Linfocitos/efectos de los fármacos , Mutágenos/toxicidad , Níquel/toxicidad , Intercambio de Cromátides Hermanas/efectos de los fármacos , Células Cultivadas , Cobre/toxicidad , Interacciones Farmacológicas , Humanos , Linfocitos/efectos de la radiación , Linfocitos/ultraestructura , Intercambio de Cromátides Hermanas/efectos de la radiación , Rayos Ultravioleta , Rayos XRESUMEN
Investigations from our laboratory and others have shown that Ni(II) treatments of cultured human lymphocytes produced a relatively small but significant increase in SCE frequency. Based on the known effects of Ni(II) on DNA replication, we evaluated whether Ni(II) produced a cell cycle delay in lymphocytes. Human lymphocytes of three normal subjects were exposed to 5, 10, and 25 microM of NiSO4 in culture medium and scored for the percent of metaphases in the first (M1), second (M2), and third (M3) cell cycle for harvest times spaced every 4 h from 36 to 72 h after culture initiation. Cell cycle duration was studied using Tice's BISACK method with certain modifications. All three doses of NiSO4 caused a delay of nearly 1.5 h in the initiation of cell division, but only 25 microM NiSO4 caused a lengthening in the cell cycle time of nearly 4 h for completion of the first cycle. Only at the highest dose of Ni(II) was there a significant increase in the SCE frequency compared to the control. When the proliferation rate index (PRI) was examined, the effect of 5 or 10 microM Ni(II) was negligible while the 25 microM concentration caused a suppression in the proliferation rate. The effect of Ni(II) on the cell cycle was much more pronounced than on the PRI. A significant increase in SCE frequency was observed only for the concentration of Ni(II) that caused a pronounced cell cycle delay, a result that is consistent with prior studies showing higher SCE responses for chemical treatments that lengthen the cell cycle.
Asunto(s)
Ciclo Celular/efectos de los fármacos , Linfocitos/efectos de los fármacos , Níquel/toxicidad , Intercambio de Cromátides Hermanas/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Linfocitos/citología , Linfocitos/ultraestructuraRESUMEN
Sister chromatid exchanges (SCE) have been examined in human lymphocytes following in vitro treatments with metal salts, nickel sulfate, lead sulfate and sodium arsenite. All of the metal salts produced significant increases in the SCE frequencies over the levels for untreated lymphocytes. The SCE frequencies were also examined for metal treatments combined with ultraviolet light (200 ergs/mm2). For the lead treatments combined with the UV dose selected, an additive SCE response was observed compared to the SCE responses for UV or metal alone. The nickel and arsenite treatments combined with UV produced a less than additive SCE response for most concentrations tested. These results suggest that nickel or arsenite present in complex mixtures may reduce the SCE response to other compounds in the mixture normally capable of producing a much stronger SCE response and therefore lead to an underestimate of the effects of chemical exposure.