Lung cancer mortality and iron oxide exposure in a French steel-producing factory.

OBJECTIVE: To study the possible association between iron oxide exposures and lung cancer risk among workers in a French carbon steel-producing factory. METHODS: 16 742 males and 959 females ever employed for at least 1 year between 1959 and 1997 were followed up for mortality from January 1968 to December 1998. Causes of death were ascertained from death certificates. Job histories and smoking habits were available for 99.7% and 72.3% of subjects, respectively. Occupational exposures were assessed by a factory-specific job-exposure matrix (JEM) validated with atmospheric measurements. Standardised mortality ratios (SMRs) were computed using local death rates (external references). Poisson regressions were used to estimate the relative risks (RRs) for occupational exposures (internal references), adjusted on potential confounding factors. RESULTS: Among males, observed mortality was lower than expected for lung cancer compared to the local population (233 deaths, SMR 0.89, 95% CI 0.78 to 1.01) and higher than expected compared to the French population (SMR 1.30, 95% CI 1.15 to 1.48) No lung cancer excess was observed for exposure to iron oxides (RR 0.80, 95% CI 0.55 to 1.17) and no dose-response relationship with intensity, duration of exposure or cumulative index was found. A significant bladder cancer excess was observed among workers exposed to oil mist (RR 2.44, 95% CI 1.06 to 5.60), increasing significantly with intensity, duration of exposure and cumulative index. CONCLUSION: This study did not detect any relationship between exposure to iron oxides and lung cancer mortality. An excess of mortality from bladder cancer was found among workers exposed to oil mist.

Crystal and electronic structures of magnesium(II), copper(II), and mixed magnesium(II)-copper(II) complexes of the quinoline half of styrylquinoline-type HIV-1 integrase inhibitors.

A new target in AIDS therapy development is HIV-1 integrase (IN). It was proven that HIV-1 IN required divalent metal cations to achieve phosphodiester bond cleavage of DNA. Accordingly, all newly investigated potent IN inhibitors contain chemical fragments possessing a high ability to chelate metal cations. One of the promising leads in the polyhydroxylated styrylquinolines (SQLs) series is (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinoline carboxylic acid (1). The present study focuses on the quinoline-based progenitor (2), which is actually the most probable chelating part of SQLs. Conventional and synchrotron low-temperature X-ray crystallographic studies were used to investigate the chelating power of progenitor 2. Mg2+ and Cu2+ cations were selected for this purpose, and three types of metal complexes of 2 were obtained: Mg(II) complex (4), Cu(II) complex (5) and mixed Mg(II)-Cu(II) complexes (6 and 7). The analysis of the crystal structure of complex 4 indicates that two tridentate ligands coordinate two Mg2+ cations, both in octahedral geometry. The Mg-Mg distance was found equal to 3.221(1) A, in agreement with the metal-metal distance of 3.9 A encountered in the crystal structure of Escherichia coli DNA polymerase I. In 5, the complex is formed by two bidentate ligands coordinating one copper ion in tetrahedral geometry. Both mixed Mg(II)-Cu(II) complexes, 6 and 7 exhibit an original arrangement of four ligands linked to a central heterometallic cluster consisting of three octahedrally coordinated magnesium ions and one tetrahedrally coordinated copper ion. Quantum mechanics calculations were also carried out in order to display the electrostatic potential generated by the dianionic ligand 2 and complex 4 and to quantify the binding energy (BE) during the formation of the magnesium complex of progenitor 2. A comparison of the binding energies of two hypothetical monometallic Mg(II) complexes with that found in the bimetallic magnesium complex 4 was made.