PubMed · 8825835
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S Lee. 1995. Polypharmacy.. https://pubmed.ncbi.nlm.nih.gov/8825835/
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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.
Germinated conidia of the thermophilic fungus Humicola grisea var. thermoidea were transformed to hygromycin B resistance using the plasmid pAN7.1. Transformation was achieved using lithium acetate treatment or electroporation. The efficiency of transformation was up to 32 and 25 transformants per microgram of plasmid DNA with the two methods, respectively. Transformants obtained by the lithium acetate method were more stable and showed a high copy number of the hph gene integrated into their genome. The other transformants, from the electroporation procedure, were stable, but unable to grow in the presence of high levels of hygromycin, and detection of the hph gene was only possible by polymerase chain reaction analysis.
Effects of melatonin priming of neutrophils and subsequent increase of phorbol 12-miristate 13-acetate stimulated respiratory burst were investigated on the modulation of L-selectin shedding and MAC-1 upregulation. Respiratory burst related H2O2 production and adhesion molecule expression were quantified by flow cytometry. Phorbol 12-miristate 13-acetate dose dependence of intracellular oxidation and adhesion molecule expression showed no relationship between respiratory burst intensity and MAC-1 expression or L-selectin shedding. Treatment of cells with 12.5 nM phorbol 12-miristate 13-acetate resulted in less than 20% of the respiratory burst response, however it induced 91.7% of total MAC-1 expression and 62.8% of L-selectin shedding. Melatonin priming experiments showed also no connection between the extent of respiratory burst and MAC-1 expression, however melatonin priming almost completely prevented L-selectin down-regulation elicited by phorbol 12-miristate 13-acetate, without affecting MAC-1 expression. It is suggested that melatonin may inhibit metalloproteases responsible for L-selectin cleavage.