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Incomplete combustion processes in diesel engines produce particulate matter (PM) that significantly contributes to air pollution. Currently, there remains a knowledge gap in relation to the physical and chemical characteristics and also the biological reactivity of the PM emitted from old- and new-generation diesel vehicles. In this study, the emissions from a Euro 3 diesel vehicle were compared to those from a Euro 6 car during the regeneration of a diesel particulate filter (DPF). Different driving cycles were used to collect two types of diesel exhaust particles (DEPs). The particle size distribution was monitored using an engine exhaust particle sizer spectrometer and an electrical low-pressure impactor. Although the Euro 6 vehicle emitted particulates only during DPF regeneration that primarily occurs for a few minutes at high speeds, such emissions are characterized by a higher number of ultrafine particles (<0.1 mu m) compared to those from the Euro 3 diesel vehicle. The emitted particles possess different characteristics. For example, Euro 6 DEPs exhibit a lower PAH content than do Euro 3 samples; however, they are enriched in metals that were poorly detected or undetected in Euro 3 emissions. The biological effects of the two DEPs were investigated in human bronchial BEAS-2B cells exposed to 50 mu g/mL of PM (corresponding to 5.2 mu g/cm(2)), and the results revealed that Euro 3 DEPs activated the typical inflammatory and procarcinogenic pathways induced by combustion-derived particles, while Euro 6 DEPs were less effective in regard to activating such biological responses. Although further investigations are required, it is evident that the different in vitro effects elicited by Euro 3 and Euro 6 DEPs can be correlated with the variable chemical compositions (metals and PAHs) of the emitted particles that play a pivotal role in the inflammatory and carcinogenic potential of airborne PM.

Purpose: Breast cancer-predisposing mutations PALB2 c.1027C>T (p.Gln343*) and PALB2 c.2167_2168delAT have each been observed multiple times in breast cancer families of Italian ancestry. More recently, the c2167_2168delAT mutation was identified in unrelated breast cancer cases of various ancestries. For each mutation, we investigated whether the origin was multiple mutational events (a “hot-spot”) or a single event (a founder allele). Methods: We genotyped and reconstructed haplotypes for 36 participants of Italian, Italian-American, Hispanic, and Nigerian ancestries, using seven short tandem repeat (STR) markers that covered 3 Megabases within and flanking PALB2 on chromosome 16. Results: For PALB2 c.1027C>T, a shared haplotype with a minimum size of 150 kb was shared by all 19 carriers investigated, all of Italian ancestry. This result suggests that this allele arose as a single event in a shared ancestor. For PALB2 c.2167_2168delAT, all 12 carriers from American-Italian and Italian families shared a 1-Mb haplotype, the 3 Hispanic carriers shared a different haplotype of size 2 Mb, and the Nigerian carrier had different alleles at all 7 STR markers. These results suggest that PALB2 c.2167_2168delAT arose multiple times, but that within each population, PALB2 c.2167_2168delAT likely represents a single mutational event. Conclusion: We identified two PALB2 mutations that are founder alleles in Italian families, one of which is, independently, also a founder mutation in American-Hispanic breast cancers.

Purpose: Even particulate matter (PM) mass concentration is the reference parameter for air quality legislation, the significance of ultrafine particles (UFP) is becoming more prominent. UFP highly contribute to the number of PM, but very little to mass. Numerous toxicological studies have shown specific UFP characteristics and reactivity, including high lung deposition efficiency, enhanced induction of inflammatory and oxidative stress processes. Among UFP different sources emission, diesel and biomass combustion processes are the most important in the north of Italy. Methods: UFP produced by diesel engines and biomass combustion were sampled adapting standardized procedures. Sampling of particles on Teflon filters has required filter holders modifications to avoid critical pressure drops. The chemical (organic compounds and metals) and physical (shape and dimensions) particles properties have been characterized. The human pulmonary BEAS-2B cell line has been used to assess the UFP effects. Results: Particles dimensions showed a mean diameter lower than 100 nm and the tendency to form aggregates. Interestingly fly ashes particles were observed in biomass burning samples. These particles were composedmainly of potassium salts and were water soluble. Diesel UFP were characterized by a high content of phenanthrene, fluoranthene and pyrene while biomass UFP showed a significant content of chrysene too. Iron, aluminum and zinc were the most abundant metals deter- mined in diesel UFP, even a significant content of chromium, nickel and platinum was observed. UFP biomass showed a significant quantity of zinc and manganese. The results of in vitro experiments showed that concentrations up to 100 g/ml of UFP for 24 h did not affect cell viability. Two non-cytotoxic concentrations, 25 and 50 g/ml have been selected for subsequent experiments. 25 g/ml at 24 h of exposure produced a significant increase of antioxidant (GCLM, NDRG1, NQO1, TXNRD1) and extracellular matrix (MMP1)

Diesel combustion and solid biomass burning are the major sources of ultrafine particles (UFP) in urbanized areas. Cardiovascular and pulmonary diseases, including lung cancer, are possible outcomes of combustion particles exposure, but differences in particles properties seem to influence their biological effects. Here the physico-chemical properties and biological effects of diesel and biomass particles, produced under controlled laboratory conditions, have been characterized. Diesel UFP were sampled from a Euro 4 light duty vehicle without DPF fuelled by commercial diesel and run over a chassis dyno. Biomass UFP were collected from a modern automatic 25 kW boiler propelled by prime quality spruce pellet. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images of both diesel and biomass samples showed aggregates of soot particles, but in biomass samples ash particles were also present. Chemical characterization showed that metals and PAHs total content was higher in diesel samples compared to biomass ones. Human bronchial epithelial (HBEC3) cells were exposed to particles for up to 2 weeks. Changes in the expression of genes involved in xenobiotic metabolism were observed after exposure to both UFP already after 24 h. However, only diesel particles modulated the expression of genes involved in inflammation, oxidative stress and epithelial-to-mesenchymal transition (EMT), increased the release of inflammatory mediators and caused phenotypical alterations, mostly after two weeks of exposure. These results show that diesel UFP affected cellular processes involved in lung and cardiovascular diseases and cancer. Biomass particles exerted low biological activity compared to diesel UFP. This evidence emphasizes that the study of different emission sources contribution to ambient PM toxicity may have a fundamental role in the development of more effective strategies for air quality improvement.