Association Between miR-148a and DNA Methylation Profile in Individuals Exposed to Lead (Pb).

Experimental and epidemiologic studies have shown that lead (Pb) is able to induce epigenetic modifications, such as changes in DNA methylation profiles, in chromatin remodeling, as well as the expression of non-coding RNAs (ncRNAs). However, very little is known about the interactions between microRNAs (miRNAs) expression and DNA methylation status in individuals exposed to the metal. The aim of the present study was to investigate the impact of hsa-miR-148a expression on DNA methylation status, in 85 workers exposed to Pb. Blood and plasma lead levels (BLL and PLL, respectively) were determined by ICP-MS; expression of the miRNA-148a was quantified by RT-qPCR (TaqMan assay) and assessment of the global DNA methylation profile (by measurement of 5-methylcytosine; % 5-mC) was performed by ELISA. An inverse association was seen between miR-148a and % 5-mC DNA, as a function of BLL and PLL (ß = -3.7; p = 0.071 and ß = -4.1; p = 0.049, respectively) adjusted for age, BMI, smoking, and alcohol consumption. Taken together, our study provides further evidence concerning the interactions between DNA methylation profile and miR-148a, in individuals exposed to Pb.

Lead (Pb) exposure induces disturbances in epigenetic status in workers exposed to this metal.

Previous studies showed that lead (Pb) exposure may modulate gene expression by changes in the epigenetic status. However, little is known about the impact of Pb exposure and alterations on DNA methylation patterns in humans exposed to this metal. The aim of this study was to assess the consequences of exposure to Pb on DNA global methylation, in order to gain a better understanding of the interactions between Pb exposure and epigenetic effects. The study included 100 male workers employed in automotive battery factories from Paraná State, Brazil. Concentrations of Pb in blood (B-Pb) and plasma (P-Pb) were determined by ICP-MS, the percentage (%) of global DNA methylation was determined by quantification of 5-methylcytosine using indirect ELISA, and sociodemographic data collected by questionnaire by trained interviewers. The mean age was 37 ± 10 (18-67 years); 18% of participants were smokers, while 32% reported consumption of alcoholic beverages. The B-Pb and P-Pb levels were 20 ± 11 and 0.56 ± 0.64 µg/dl, respectively; % global DNA methylation was 2.8 ± 1.1% (ranging from 1.1 to 6.5%). B-Pb and P-Pb concentrations were significantly correlated. Furthermore, a marked association was noted between Pb biomarkers and DNA global methylation. Taken together, our data demonstrated that Pb exposure induced alterations on DNA global methylation in workers who were exposed to the metal and consequently may result in disturbances in the regulation of gene expression, leading to potentially several health adverse effect outcomes.

Detection of human T-cell lymphotropic virus type 1 in plasma samples.

Human T-cell lymphotropic virus type 1 (HTLV-1) is an RNA virus responsible for diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATL). Cell-to-cell contact and Tax-induced clonal expansion of infected cells are the main modes of virus replication, making virus detection during the viremic stage difficult. Consequently, the proviral load is the current virologic marker for disease monitoring, but the mechanisms of progression have not been established yet. Thus, this study investigated the presence of virus in plasma from asymptomatic HTLV-1 carriers and from HAM/TSP patients. Real-time PCR was performed on DNA from 150 plasma samples; 12 (8%) had detectable DNA amplification, including 6 (4%) asymptomatic HTLV-1 carriers and 14 (26%) HAM/TSP patients (p<0.005). Of the 33 samples submitted for nested PCR, six (18%, p=0.02) were positive for HTLV-1 RNA in the plasma. Additionally, 26 plasma samples were treated with DNAse enzyme to eliminate any DNA contamination before RNA extraction. Two of them (8%) showed amplification for HTLV-1 (p=0.5). Therefore, this study described for the first time the detection of free HTLV-1 RNA in plasma from HTLV-1-infected subjects, regardless of their clinical status. Thus, HTLV-1 viral replication does occur in plasma, and other transmission pathways for HTLV-1 should be investigated further.