Читать книгу Genomic and Epigenomic Biomarkers of Toxicology and Disease - Группа авторов - Страница 57

Elemental lead (Pb) is found in lead ore deposits that are distributed throughout the world (Abadin et al. 2007). Lead does not degrade in the environment and is dispersed worldwide as a result of anthropogenic activities such as mining and smelting ore, the manufacture of lead-containing products (lead-containing gasoline, paints, batteries, radiation shields, water pipes, ammunition, ceramics and metal containers), the combustion of coal and oil, and waste incineration (Tokar et al. 2013). Lead is listed as one of the topmost toxic substances, and its toxic properties have been recognized for over 2,000 years (Abadin et al. 2007). However, in the last few decades, there has been increased awareness about the detrimental health effects of low-level lead exposure, particularly in children. This awareness has prompted changes in public health policies, and the result the is phasing out of lead from several sources, including gasoline and paints. Nonetheless, exposure to lead still occurs, primarily from lead-containing paint and water pipes present in older housing, from residues along roadways, or in the form of occupational exposure.

For the general population, lead exposure occurs orally for the most part; however, inhalation and dermal contact can also occur, albeit rarely, in occupational settings. The health effects caused by lead exposure are diverse (neurological, cardiovascular, renal, hematological, reproductive, developmental, respiratory, hepatic, endocrine, gastrointestinal, musculoskeletal, ocular, and cancer) and depend on numerous factors including age, nutritional status, and life stage (e.g., in utero).

The blood lead reference value was set at 5 µg/dL in 2012; elevated lead in blood is an indication of excessive exposure (CDC 2012). The most common metric for lead exposure is the concentration of lead in blood, although other measurements of lead in urine, bone, and hair can be used to quantitate exposure (Abadin et al. 2007). Levels of lead in plasma and semen are difficult to measure because lead concentrations in these fluids are often near the lower limits of detection, and lead measurements in saliva and sweat show inconsistent results when compared to blood lead.

Circulating miRNAs associated with lead exposure have been identified in humans (Mitra et al. 2021; Xu et al. 2017, de Araujo et al. 2021). In a large study that analyzed 1,130 Chinese workers with occupational lead exposure, miRNA microarray analyses from plasma identified three miRNAs that were significantly downregulated (miR-520c-3p, miR-148a, and miR-211) and one miRNA that was significantly upregulated (miR-572) in workers chronically exposed to lead who also had high blood lead levels (BLLs) (51.35 ± 6.86 µg/dL; see Xu et al. 2017). However, workers with high BLLs were compared to workers with low BLLs (8.93 ± 1.53 µg/dL), which still contain levels above the blood lead reference values set by the Centers for Disease Control (CDC). Thus it is unclear whether the changes in circulating miRNA expression are a function of lead exposure or happen only when a specific exposure threshold is breached. In another study, which analyzed workers who suffered from occupational lead exposure in Northern India, expression levels of circulating miR-20b-5, miR-221-3p (miR-221), miR-155-5p (miR-155), miR-20b from serum were quantified by RT-qPCR and compared to expression levels in individuals without any history of occupational lead exposure (Mitra et al. 2021). Circulating miR-221 and miR-155 were significantly higher in lead-exposed workers than in non-exposed individuals. In a third study, circulating miRNA expression profiles were measured in blood using RT-qPCR from battery plant workers from Paraná State, Brazil and revealed an association of DNA methylation status and miR-148a expression in lead-exposed workers (de Araujo et al. 2021). However, no unexposed control population was included in this study. Although the de Araujo study correlated circulating miR-148a to DNA methylation status in lead-exposed workers only, DNA methylation increased with the lead dose and miR-148a expression was inversely correlated to DNA methylation. Taken together, circulating miRNA analyses from two small populations of lead-exposed workers revealed that several circulating miRNAs are differentially expressed as a result of lead exposure; thus, pending further validation, these miRNAs hold promise for being used as biomarkers.