Biomonitoring of a population of Portuguese workers exposed to lead.

Lead is a heavy metal that has been used for many centuries and it is still used for various industrial purposes thanks to its physical and chemical characteristics. Human exposure to lead can result in a wide range of biological effects depending upon the level and duration of exposure. Despite the fact that lead has been found capable of eliciting genotoxic responses in a wide range of tests, not all studies have been conclusive. Although several experimental studies have shown that lead may modulate immune responses, data in exposed humans are still preliminary. The purpose of our study was to evaluate the genotoxic and immunotoxic effects of lead exposure in a group of 70 male workers from two Portuguese factories. The control group comprised 38 healthy males. The exposed individuals showed significantly higher levels of lead in blood and zinc protoporphyrin, and significantly lower δ-aminolevulinic acid dehydratase activity than the controls, suggesting a relatively high lead exposure. Nevertheless, the limit of 70 µg/dl for lead in blood established by the Portuguese regulation was never reached. Results of the comet assay were not modified by the exposure, but a significant increase in the mutation frequency in the exposed workers was obtained in the T-cell receptor mutation assay. Furthermore, data obtained in the analysis of the different lymphocyte subsets showed a significant decrease in %CD8+ cells and a significant increase in the %CD4+/%CD8+ ratio in exposed individuals with regard to the controls. No clear effect was observed for vitamin D receptor genetic polymorphism on the parameters evaluated. In view of our results showing mutagenic and immunotoxic effects related to lead exposure in occupational settings, it seems that the Portuguese biological exposure limit for lead needs to be revised in order to increase the safety of exposed workers.

Genotoxic effects of occupational exposure to lead and influence of polymorphisms in genes involved in lead toxicokinetics and in DNA repair.

Lead is still widely used in many industrial processes and is very persistent in the environment. Although toxic effects caused by occupational exposure to lead have been extensively studied, there are still conflicting results regarding its genotoxicity. In a previous pilot study we observed some genotoxic effects in a population of lead exposed workers. Thus, we extended our study analysing a larger population, increasing the number of genotoxicity endpoints, and including a set of 20 genetic polymorphisms related to lead toxicokinetics and DNA repair as susceptibility biomarkers. Our population comprised 148 workers from two Portuguese factories and 107 controls. The parameters analysed were: blood lead levels (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity as exposure biomarkers, and T-cell receptor (TCR) mutation assay, micronucleus (MN) test, comet assay and OGG1-modified comet assay as genotoxicity biomarkers. Lead exposed workers showed markedly higher BLL and lower ALAD activity than the controls, and significant increases of TCR mutation frequency (TCR-Mf), MN rate and DNA damage. Oxidative damage did not experience any significant alteration in the exposed population. Besides, significant influence was observed for VDR rs1544410 polymorphism on BLL; APE1 rs1130409 and LIG4 rs1805388 polymorphisms on TCR-Mf; MUTYH rs3219489, XRCC4 rs28360135 and LIG4 rs1805388 polymorphisms on comet assay parameter; and OGG1 rs1052133 and XRCC4 rs28360135 polymorphisms on oxidative damage. Our results showed genotoxic effects related to occupational lead exposure to levels under the Portuguese regulation limit of 70 µg/dl. Moreover, a significant influence of polymorphisms in genes involved in DNA repair on genotoxicity biomarkers was observed.

A Retrospective bacteriological study of mycobacterial infections in patients with acquired immune deficiency syndrome (AIDS)

The main species of mycobacteria isolated in 51 patients with acquired immunodeficiency syndrome (AIDS) admitted to the Clinical Hospital of UNICAMP (Teaching Hospital) in 1996, were studied retrospectively by recording the isolation site and signs of pathogenesis. Of these isolates, 31 (55 percent) were M.tuberculosis and 20 (45 percent) M.avium complex. Strains of M.tuberculosis isolated in 1996, 1997, and 1998, originating from 42 patients who had AIDS, were tested for susceptibillity to isoniazid and rifampicin. Of these, 34 (81 percent) were susceptible to both drugs tested, 4 (10 percent) were resistant to isoniazid and susceptible to rifampicin, 2 (5 percent) were susceptible to isoniazid and resistant to rifampicin, and 2 (5 percent) were resistant to both rifampicin and isoniazid. We conclude that, in Brazil, M.avium complex infections in AIDS are more commun that has been previously suggested; i.e., almost as frequent as M.tuberculosis infections. Approximately 20 percent of M.tuberculosis strains showed resistence to rifampicin and/or isomiazid. Further distribution of information regarding how to treat the disease in AIDS patients is needed.