A systematic review of cancer risk among users of smokeless tobacco (Swedish snus) exclusively, compared with no use of tobacco.

The main objective of this systematic review was to assess cancer risk, and mortality after cancer diagnosis, for exclusive users of Swedish snus, compared with non-users of tobacco. We followed international standards for systematic reviews and graded our confidence in the risk estimates using the GRADE approach. Our search gave 2450 articles, of which 67 were assessed in full text against our inclusion criteria. Of these, 14 cohort-studies and one case-control study were included in the review. The studies investigated risk of cancer in the oral cavity or oropharynx (3 studies), esophagus (1 study), stomach (1 study), pancreas (2 studies), colorectum (2 studies), anus (1 study) and lung (1 study), as well as malignant lymphoma (1 study), leukemia and multiple myeloma (1 study), melanoma (1 study), any cancer (1 study) and mortality after cancer diagnosis (4 studies). Cancer risk could only be evaluated in men as there was a general lack of data for women. All included studies were evaluated to have a moderate risk of bias, mostly related to validity of exposure information. An increased risk of cancer of the esophagus, pancreas, stomach and rectum as well as an association between use of snus and increased mortality after a cancer diagnosis was reported. Our confidence in the various risk estimates varied from moderate through low to very low.

Developmental neurotoxicity of acrylamide and its metabolite glycidamide in a human mixed culture of neurons and astrocytes undergoing differentiation in concentrations relevant for human exposure.

Neural stem cells (NSCs) derived from human induced pluripotent stem cells were used to investigate effects of exposure to the food contaminant acrylamide (AA) and its main metabolite glycidamide (GA) on key neurodevelopmental processes. Diet is an important source of human AA exposure for pregnant women, and AA is known to pass the placenta and the newborn may also be exposed through breast feeding after birth. The NSCs were exposed to AA and GA (1 ×10-8 - 3 ×10-3 M) under 7 days of proliferation and up to 28 days of differentiation towards a mixed culture of neurons and astrocytes. Effects on cell viability was measured using Alamar Blue™ cell viability assay, alterations in gene expression were assessed using real time PCR and RNA sequencing, and protein levels were quantified using immunocytochemistry and high content imaging. Effects of AA and GA on neurodevelopmental processes were evaluated using endpoints linked to common key events identified in the existing developmental neurotoxicity adverse outcome pathways (AOPs). Our results suggest that AA and GA at low concentrations (1 ×10-7 - 1 ×10-8 M) increased cell viability and markers of proliferation both in proliferating NSCs (7 days) and in maturing neurons after 14-28 days of differentiation. IC50 for cell death of AA and GA was 5.2 × 10-3 M and 5.8 × 10-4 M, respectively, showing about ten times higher potency for GA. Increased expression of brain derived neurotrophic factor (BDNF) concomitant with decreased synaptogenesis were observed for GA exposure (10-7 M) only at later differentiation stages, and an increased number of astrocytes (up to 3-fold) at 14 and 21 days of differentiation. Also, AA exposure gave tendency towards decreased differentiation (increased percent Nestin positive cells). After 28 days, neurite branch points and number of neurites per neuron measured by microtubule-associated protein 2 (Map2) staining decreased, while the same neurite features measured by ßIII-Tubulin increased, indicating perturbation of neuronal differentiation and maturation.

Biological effects of combustion-derived particles from different biomass sources on human bronchial epithelial cells.

Combustion-derived particles (CDPs), in particular from traffic, are regarded as a central contributor for adverse health effects linked to air pollution. Recently, also biomass burning has been recognized as an important source for CDPs. Here, the effects of CDPs (PM10) originating from burning of pellet, charcoal and wood on key processes associated to lung carcinogenesis were explored. Human bronchial epithelial cells (HBEC3-KT) were exposed to 2.5 µg/cm2 of CDPs for 24 h and biological effects were examined in terms of cytotoxicity, inflammation, epithelial to mesenchymal transition (EMT)-related effects, DNA damage and genotoxicity. Reduced cell migration, inflammation and modulation of various PM-associated genes were observed mainly after exposure to wood and pellet. In contrast, only particles from pellet burning induced alteration in cell proliferation and DNA damage, which resulted in cell cycle alterations. Charcoal instead, appeared in general less effective in inducing pro-carcinogenic effects. These results illustrate differences in the toxicological profile due to the CDPs source. The different chemical compounds adsorbed on CDPs seemed to be central for particle properties, leading to an activation of various cellular signaling pathways involved in early steps of cancer progression.

Phthalate levels in Norwegian indoor air related to particle size fraction.

Phthalates are found in numerous consumer products, including interior materials like polyvinyl chloride (PVC). Several studies have identified phthalates in indoor air. A recent case-control study demonstrated associations between allergic symptoms in children and the concentration of phthalates in dust collected from their homes. Here we have analyzed the content of selected phthalates in particulate matter (PM): PM(10) and PM(2.5) filter samples collected in 14 different indoor environments. The results showed the presence of the phthalates di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP), dicyclohexyl phthalate (DCHP) and diethyl hexyl phthalate (DEHP) in the samples. The dominating phthalate in both PM(10) and PM(2.5) samples from all locations was DBP. More than a 10-fold variation in the mean concentration of total phthalates between sampling sites was observed. The highest levels of total phthalates were detected in one children's room, one kindergarten, in two primary schools, and in a computer room. The relative contribution of total phthalates in PM(10) and PM(2.5) was 1.1 +/- 0.3% for both size fractions. The contribution of total phthalates in PM(2.5) to total phthalates in PM(10) ranged from 23-81%, suggesting different sources. Of the phthalates that were analyzed in the PM material, DBP was found to be the major phthalate in rubber from car tyres. However, our analyses indicate that tyre wear was of minor importance for indoor levels of both DBP as well as total phthalates. Overall, these results support the notion that inhalation of indoor PM contributes to the total phthalate exposure.