Trace and Major Element Concentrations in Cadaveric Lung Tissues from World Trade Center Health Registry Decedents and Community Controls.

Studies of the health impacts of the 11 September 2001 terrorist attacks on New York City's (NYC's) World Trade Center (WTC) towers have been hindered by imprecise estimates of exposure. We sought to identify potential biomarkers of WTC exposure by measuring trace and major metal concentrations in lung tissues from WTC-exposed individuals and less exposed community controls. We also investigated associations of lung tissue metal concentrations with self-reported exposure and respiratory symptoms. The primary analyses contrasted post-mortem lung tissue concentrations obtained from autopsies in 2007-2011 of 76 WTC Health Registry (WTCHR) enrollees with those of 55 community controls. Community controls were frequency-matched to WTCHR decedents by age at death, calendar quarter of death, gender, race, ethnicity and education and resided at death in NYC zip codes less impacted by WTC dust and fumes. We found WTCHR decedents to have significantly higher iron (Fe) lung tissue concentrations than community controls. Secondary analyses among WTCHR decedents adjusted for sex and age showed the log(molybdenum (Mo)) concentration to be significantly associated with non-rescue/recovery exposure. Post hoc analyses suggested that individuals whose death certificates listed usual occupation or industry as the Sanitation or Police Departments had elevated lung tissue Fe concentrations. Among WTCHR decedents, exposure to the WTC dust cloud was significantly associated with elevated lung tissue concentrations of titanium (Ti), chromium (Cr) and cadmium (Cd) in non-parametric univariable analyses but not in multivariable analyses adjusted for age and smoking status. Logistic regression adjusted for age and smoking status among WTCHR decedents showed one or more respiratory symptoms to be positively associated with log (arsenic (As)), log(manganese (Mn)) and log(cobalt (Co)) concentrations, while new-onset wheezing and sinus problems were negatively associated with log(Fe) concentration. Fe concentrations among individuals with wheezing, nonetheless, exceeded those in community controls. In conclusion, these data suggest that further research may be warranted to explore the utility as biomarkers of WTC exposure of Fe in particular and, to a lesser extent, Mo, Ti, Cr and Cd in digestions of lung tissue.

DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol.

The allure of tobacco smoking is linked to the instant gratification provided by inhaled nicotine. Unfortunately, tobacco curing and burning generates many mutagens including more than 70 carcinogens. There are two types of mutagens and carcinogens in tobacco smoke (TS): direct DNA damaging carcinogens and procarcinogens, which require metabolic activation to become DNA damaging. Recent studies provide three new insights on TS-induced DNA damage. First, two major types of TS DNA damage are induced by direct carcinogen aldehydes, cyclic-1,N2-hydroxy-deoxyguanosine (γ-OH-PdG) and α-methyl-1, N2-γ-OH-PdG, rather than by the procarcinogens, polycyclic aromatic hydrocarbons and aromatic amines. Second, TS reduces DNA repair proteins and activity levels. TS aldehydes also prevent procarcinogen activation. Based on these findings, we propose that aldehydes are major sources of TS induce DNA damage and a driving force for carcinogenesis. E-cigarettes (E-cigs) are designed to deliver nicotine in an aerosol state, without burning tobacco. E-cigarette aerosols (ECAs) contain nicotine, propylene glycol and vegetable glycerin. ECAs induce O6-methyl-deoxyguanosines (O6-medG) and cyclic γ-hydroxy-1,N2--propano-dG (γ-OH-PdG) in mouse lung, heart and bladder tissues and causes a reduction of DNA repair proteins and activity in lungs. Nicotine and nicotine-derived nitrosamine ketone (NNK) induce the same types of DNA adducts and cause DNA repair inhibition in human cells. After long-term exposure, ECAs induce lung adenocarcinoma and bladder urothelial hyperplasia in mice. We propose that E-cig nicotine can be nitrosated in mouse and human cells becoming nitrosamines, thereby causing two carcinogenic effects, induction of DNA damage and inhibition of DNA repair, and that ECA is carcinogenic in mice. Thus, this article reviews the newest literature on DNA adducts and DNA repair inhibition induced by nicotine and ECAs in mice and cultured human cells, and provides insights into ECA carcinogenicity in mice.