Airborne particulate matter and mitochondrial damage: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Oxidative stress generation is a primary mechanism mediating the effects of Particulate Matter (PM) on human health. Although mitochondria are both the major intracellular source and target of oxidative stress, the effect of PM on mitochondria has never been evaluated in exposed individuals.</p> <p>Methods</p> <p>In 63 male healthy steel workers from Brescia, Italy, studied between April and May 2006, we evaluated whether exposure to PM was associated with increased mitochondrial DNA copy number (MtDNAcn), an established marker of mitochondria damage and malfunctioning. Relative MtDNAcn (RMtDNAcn) was determined by real-time PCR in blood DNA obtained on the 1^st(time 1) and 4^thday (time 2) of the same work week. Individual exposures to PM₁₀, PM₁, coarse particles (PM₁₀-PM₁) and airborne metal components of PM₁₀(chromium, lead, arsenic, nickel, manganese) were estimated based on measurements in the 11 work areas and time spent by the study subjects in each area.</p> <p>Results</p> <p>RMtDNAcn was higher on the 4^thday (mean = 1.31; 95%CI = 1.22 to 1.40) than on the 1^stday of the work week (mean = 1.09; 95%CI = 1.00 to 1.17). PM exposure was positively associated with RMtDNAcn on either the 4^th(PM₁₀: β = 0.06, 95%CI = -0.06 to 0.17; PM₁: β = 0.08, 95%CI = -0.08 to 0.23; coarse: β = 0.06, 95%CI = -0.06 to 0.17) or the 1^stday (PM₁₀: β = 0.18, 95%CI = 0.09 to 0.26; PM₁: β = 0.23, 95%CI = 0.11 to 0.35; coarse: β = 0.17, 95%CI = 0.09 to 0.26). Metal concentrations were not associated with RMtDNAcn.</p> <p>Conclusions</p> <p>PM exposure is associated with damaged mitochondria, as reflected in increased MtDNAcn. Damaged mitochondria may intensify oxidative-stress production and effects.</p

Common Molecular Etiologies Are Rare in Nonsyndromic Tibetan Chinese Patients with Hearing Impairment

Background: Thirty thousand infants are born every year with congenital hearing impairment in mainland China. Racial and regional factors are important in clinical diagnosis of genetic deafness. However, molecular etiology of hearing impairment in the Tibetan Chinese population living in the Tibetan Plateau has not been investigated. To provide appropriate genetic testing and counseling to Tibetan families, we investigated molecular etiology of nonsyndromic deafness in this population. Methods: A total of 114 unrelated deaf Tibetan children from the Tibet Autonomous Region were enrolled. Five prominent deafness-related genes, GJB2, SLC26A4, GJB6, POU3F4, and mtDNA 12S rRNA, were analyzed. Inner ear development was evaluated by temporal CT. A total of 106 Tibetan hearing normal individuals were included as genetic controls. For radiological comparison, 120 patients, mainly of Han ethnicity, with sensorineural hearing loss were analyzed by temporal CT. Results: None of the Tibetan patients carried diallelic GJB2 or SLC26A4 mutations. Two patients with a history of aminoglycoside usage carried homogeneous mtDNA 12S rRNA A1555G mutation. Two controls were homozygous for 12S rRNA A1555G. There were no mutations in GJB6 or POU3F4. A diagnosis of inner ear malformation was made in 20.18 % of the Tibetan patients and 21.67 % of the Han deaf group. Enlarged vestibular aqueduct, the most common inner ear deformity, was not found in theTibetan patients, but was seen in 18.33 % of the Han patients. Common molecular etiologies