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In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in animals, such mutagens can therefore be carcinogens, although not all necessarily are. All mutagens have characteristic mutational signatures with some chemicals becoming mutagenic through cellular processes. The process of DNA becoming modified is called mutagenesis. Not all mutations are caused by mutagens: so-called "spontaneous mutations" occur due to spontaneous hydrolysis, errors in DNA replication, repair and recombination. Discovery The first mutagens to be identified were carcinogens, substances that were shown to be linked to cancer. Tumors were described more than 2,000 years before the discovery of chromosomes and DNA; in 500 B.C., the Greek physician Hippocrates named tumors resembling a crab karkinos (from which the w

Year-long variability of polycyclic aromatic hydrocarbons (PAHs) and their contribution on winter intense pollution events in the urban environment of Athens, Greece

Maria Apostolaki, Athanasios Nenes

Polycyclic aromatic hydrocarbons (PAHs) are organic pollutants with proven mutagenic and carcinogenic potential that originate from incomplete combustion, and partition to fine particulate matter. Nitro-PAHs & oxy-PAHs are oxidation products of PAHs with increased toxicity compared to their parent members and may reveal useful information about the aging and oxidation processes of PAHs. In this study, we investigate the seasonal profiles of 31 PAHs and select oxidized forms such as nitro PAHs & quinones in Athens, Greece to understand their sources, levels, toxicity and impacts. PAHs levels were found to be significantly higher during winter, particularly during intense pollution episodes, compared to the other seasons. Chemical markers linked to biomass burning (BB) emissions are found to correlate well with the total amount of PAHs (ΣPAHs) during wintertime, strongly indicating that BB emissions are a significant source of PAHs. Positive Matrix Factorization (PMF) analysis showed that more than 50% of ΣPAHs originate from BB emissions and that a “factor” (composed of a specific mixture of PAHs) characterizes biomass burning emissions – and can potentially be used as a tracer. Analysis of the PMF series suggests that BB aerosol is much more carcinogenic than the effects of gasoline and diesel combustion combined. Finally, the exposure impact during winter is 9 times higher compared with the other seasons.

2021

Bioassay battery interlaboratory investigation of emerging contaminants in spiked water extracts - Towards the implementation of bioanalytical monitoring tools in water quality assessment and monitoring

Bioassays are particularly useful tools to link the chemical and ecological assessments in water quality monitoring. Different methods cover a broad range of toxicity mechanisms in diverse organisms, and account for risks posed by non-target compounds and mixtures. Many tests are already applied in chemical and waste assessments, and stakeholders from the science-police interface have recommended their integration in regulatory water quality monitoring. Still, there is a need to address bioassay suitability to evaluate water samples containing emerging pollutants, which are a current priority in water quality monitoring. The presented interlaboratory study (ILS) verified whether a battery of miniaturized bioassays, conducted in 11 different laboratories following their own protocols, would produce comparable results when applied to evaluate blinded samples consisting of a pristine water extract spiked with four emerging pollutants as single chemicals or mixtures, i.e. triclosan, acridine, 17 alpha-ethinylestradiol (EE2) and 3-nitrobenzanthrone (3-NBA). Assays evaluated effects on aquatic organisms from three different trophic levels (algae, daphnids, zebrafish embryos) and mechanism-specific effects using in vitro estrogenicity (ER-Luc, YES) and mutagenicity (Ames fluctuation) assays. The test battery presented complementary sensitivity and specificity to evaluate the different blinded water extract spikes. Aquatic organisms differed in terms of sensitivity to triclosan (algae > daphnids > fish) and acridine (fish > daphnids > algae) spikes, confirming the complementary role of the three taxa for water quality assessment. Estrogenicity and mutagenicity assays identified with high precision the respective mechanism-specific effects of spikes even when non-specific toxicity occurred in mixture. For estrogenicity, although differences were observed between assays and models, EE2 spike relative induction EC50 values were comparable to the literature, and E2/EE2 equivalency factors reliably reflected the sample content. In the Ames, strong revertant induction occurred following 3-NBA spike incubation with the TA98 strain, which was of lower magnitude after metabolic transformation and when compared to TA100. Differences in experimental protocols, model organisms, and data analysis can be sources of variation, indicating that respective harmonized standard procedures should be followed when implementing bioassays in water monitoring. Together with other ongoing activities for the validation of a basic bioassay battery, the present study is an important step towards the implementation of bioanalytical monitoring tools in water quality assessment and monitoring. (C) 2016 Elsevier Ltd. All rights reserved.

Elsevier2016

Multi-resistance of human enterovirus to UV-C disinfection and mutagenic nucleoside analogs

Virginie Bachmann, Anna Carratala Ripolles, Tamar Kohn, Qingxia Zhong

Disinfection is an important strategy to control the environmental transmission of human viruses. Specifically, UV254 is increasingly used to disinfect from clinical items or surfaces to drinking water. RNA virus populations have high mutation rates and large population numbers that allow them to rapidly adapt to stressors. It is therefore likely that variants with enhanced resistance to disinfection may eventually emerge in a virus population. The genetic basis and mechanisms that underpin the emergence of virus resistance to disinfection remain, however, unknown. The goal of this study was to investigate the emergence of echoviruses resistant to UV254 disinfection in vitro, and to characterize the genotypic and phenotypic changes in the resistant populations as compared to the wild-type. Resistant virus populations emerged in mutation-accumulation laboratory experiments. Each experiment consisted in exposing echovirus suspensions to a UV254 fluence such that a 4.5 log10 reduction in infective viruses was achieved, and then regrowing the survivors by infecting BGM cells at a very low multiplicity of infection (MOI>0.001). Unexposed control experiments were conducted in parallel by diluting the virus suspensions instead of exposing them to UV254 prior to regrowth. We demonstrated that echovirus populations became increasingly resistant to UV254. Interestingly, a similar extent of resistance was observed in the unexposed control experiments. Fixed mutations were repeatedly identified by next generation sequencing in the 2C and 3D protein region, both involved in the genome replication. The wild-type and resistant echovirus populations exhibited an equivalent replicative fitness under standard culturing conditions. However, the UV254-resistant mutants were more resistant to ribavirin and guanidine hydrochloride. Finally, the exposed populations were able to maintain the production of infective progeny despite the effect of such chemical mutagens. Combined, these findings suggest that multi-resistance of echovirus to UV254 disinfection and treatment with mutagenic nucleotide analogs may arise in virus populations that, subjected to repeated dramatic bottlenecks, evolve towards an increased replication fidelity. The outcomes of this work show that enteric human pathogens may exhibit multi-resistance to disinfection and clinical antiviral therapies. Ultimately, the results from this work may impact future strategies to ensure adequate control of virus environmental transmission.

2016

Multi-resistance of human enterovirus to UV-C disinfection and mutagenic nucleoside analogs

Virginie Bachmann, Anna Carratala Ripolles, Tamar Kohn, Qingxia Zhong

2016

Elsevier2016