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Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from mice chronically exposed to 1 of 20 known or suspected human carcinogens, we reveal that most agents do not generate distinct mutational signatures or increase mutation burden, with most mutations, including driver mutations, resulting from tissue-specific endogenous processes. We identify signatures resulting from exposure to cobalt and vinylidene chloride and link distinct human signatures (SBS19 and SBS42) with 1,2,3-trichloropropane, a haloalkane and pollutant of drinking water, and find these and other signatures in human tumor genomes. We define the cross-species genomic landscape of tumors induced by an important compendium of agents with relevance to human health. A genomic analysis of tumors in mice caused by known or suspected carcinogens shows that most carcinogens do not generate distinct mutational signatures.

Background Genome streamlining is a feasible strategy for constructing an optimum microbial chassis for synthetic biology applications. Genomic islands (GIs) are usually regarded as foreign DNA sequences, which can be obtained by horizontal gene transfer among microorganisms. A model strain Pseudomonas putida KT2440 has broad applications in biocatalysis, biotransformation and biodegradation. Results In this study, the identified GIs in P. putida KT2440 accounting for 4.12% of the total genome size were deleted to generate a series of genome-reduced strains. The mutant KTU-U13 with the largest deletion was advantageous over the original strain KTU in several physiological characteristics evaluated. The mutant KTU-U13 showed high plasmid transformation efficiency and heterologous protein expression capacity compared with the original strain KTU. The metabolic phenotype analysis showed that the types of carbon sources utilized by the mutant KTU-U13 and the utilization capabilities for certain carbon sources were increased greatly. The polyhydroxyalkanoate (PHA) yield and cell dry weight of the mutant KTU-U13 were improved significantly compared with the original strain KTU. The chromosomal integration efficiencies for the γ-hexachlorocyclohexane (γ-HCH) and 1,2,3-trichloropropane (TCP) biodegradation pathways were improved greatly when using the mutant KTU-U13 as the recipient cell and enhanced degradation of γ-HCH and TCP by the mutant KTU-U13 was also observed. The mutant KTU-U13 was able to stably express a plasmid-borne zeaxanthin biosynthetic pathway, suggesting the excellent genetic stability of the mutant. Conclusions These desirable traits make the GIs-deleted mutant KTU-U13 an optimum chassis for synthetic biology applications. The present study suggests that the systematic deletion of GIs in bacteria may be a useful approach for generating an optimal chassis for the construction of microbial cell factories.

In the present era, polymeric pipes have emerged as the replacement for metallic alternatives in constructing water distribution networks within cities or homes, due to their notable flexibility and durability. Nevertheless, there have been increased concerns over the safety of consuming water that has come into contact with polymeric materials. This issue arises from the possible leaching of organic contaminants, either due to plastic deterioration or from biofilms that typically develop within polymeric pipes. These biofilms may act as a source of disinfection byproducts during water and/or system disinfection. The objective of the study was to investigate the presence of volatile organic compounds (VOCs) that could migrate from plastic plumbing pipes into tap water. For this purpose, 50 tap water samples from diferent houses within the Al-Madinah Al-Munawwarah residential area (Saudi Arabia) were collected and analysed for the occurrence of VOCs; trichloromethane (1,1,1-TCA), dichloropropane (1,2-DCP), 1,2,3-trichloropropane (1,2,3-TCP) benzyl chloride (BC) 2-nitropropane (2-NP) 2,4-dichlorophenol (2,4-DCP), 4-ethylphenol (4-EP), benzene and 2-butanone using CG-MS. The most prevalent compounds were benzene, 2-butanone, 1,1,1-TCA, 1,2-DCP, BC, and 1,2,3-TCP. These were identified in 78%, 76%, 68%, 58%, 50%, and 42% of the samples assessed, respectively. The levels of 1,2,3-TCP, benzene, 2,4-DCP and BC exceeded the allowable limit in 43%, 10%, 8% and 6% of the samples, respectively. The remaining VOCs were within the WHO standards. The analysis of water source samples revealed the presence of BC, 1,2-DCP, and 4-EP in 40%, 40%, and 30% of samples, respectively, with no other VOCs detected. This suggests that these contaminants primarily originate from polymeric pipes used in household plumbing systems.

The roles of dichloromethane (DCM) and 1,2,3-trichloropropane (1,2,3-TCP) in occupational cholangiocarcinoma, first reported in 2012, remain elusive. This study aimed to determine the potential of 1,2-dichloropropane (1,2-DCP), DCM, and 1,2,3-TCP to induce DNA damage-a hallmark of carcinogenicity-in human cholangiocytes. Monocultures of human immortalized cholangiocytes (MMNK-1 cholangiocytes) and co-cultures of MMNK-1 cholangiocytes with human THP-1 monocyte-derived macrophages and monocytes were each exposed to 1,2-DCP, DCM or 1,2,3-TCP at 0, 0.1, and 0.4 mM for 24 hours. DNA double-strand break marker γ-H2AX-positive foci and γ-H2AX pan-nuclear staining-which is known to be induced during early or intermediate stages of apoptosis or under replicative stress/checkpoint abrogation in cholangiocytes-were counted in 100 and 200 cholangiocytes, respectively. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. The increase in dense (≥55) γ-H2AX foci induced by all 3 chemical compounds was significantly greater in co-cultures with macrophages, but not with monocytes, than in monocultures. However, only 1,2-DCP decreased the number of γ-H2AX pan-nuclear-positive and TUNEL-positive cholangiocytes in co-cultures with macrophages, but not in monocultured cholangiocytes. Co-treatment with a pan-caspase inhibitor decreased the number of γ-H2AX pan-nuclear-positive cholangiocytes in each group by about 50%, suggesting that apoptotic signaling is involved, at least in part, in the induction of γ-H2AX pan-nuclear-positive cholangiocytes. Our study showed that co-culture with macrophages enhanced DNA double-strand breaks induced by all 3 tested chemical compounds, while only 1,2-DCP exhibited a proliferative effect in monocultures and anti-apoptotic effects in co-cultures with macrophages, which are key characteristics of carcinogens, thus distinguishing 1,2-DCP from DCM and 1,2,3-TCP.

In March of 2023, the first National Primary Drinking Water Standards for per- and polyfluoroalkyl substances (PFAS) were announced. The fourth Regulatory Determination that led to this development also included several other contaminants for consideration: 1,4-dioxane (dioxane), 1,2,3-trichloropropane (TCP), and strontium, which faced no determination at this time. In this study, the relative risks associated with these three contaminants and the two regulated PFAS, perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), are analyzed on a subregion level, considering socioeconomic and racial factors in national exposure and risk levels for the U.S. population. Results indicate that PFOS and PFOA represent the greatest risk to the population in the subregions in which they are detected. Considering race and ethnicity, living in a majority-minority community may be a risk factor for exposure to strontium, while minority status did not increase exposure risk for dioxane, TCP, PFOS, and PFOA. Additionally, total cancer and non-cancer relative health indicator (RHI) matrices indicate that majority-minority communities face significantly greater risks from strontium exposure. Regression models also confirm results for strontium but place the risk on racial/ethnic minority populations more specifically in regions with greater Hispanic/Latino community percentages. Finally, while greater poverty in a subregion is associated with significantly higher cancer and non-cancer RHI values for dioxane, strontium, and TCP, after controlling for state-level variations, multi-level models reveal that greater poverty is associated with significantly lower risk from these three contaminants.

Controlled thermal degradation of high-molecular-weight poly-3-hydroxybutyrate (PHB) was studied in dimethylformamide (DMF), bromoform, tetrabromoethane, and trichloropropane. Samples with molecular weights of 1.6 kDa and higher were obtained. PHB degradation in pure DMF and in trichloropropane resulted in the formation of C-terminal crotonic acid residues at the sites of polymer chain scission. In the case of bromoform and tetrabromoethane, 3-bromobutyric acid residues were formed (61–68% at 100 °C and 29–54% at 145 °C), along with crotonic acid residues. This indicates the possibility of halogen capture from solvent molecules at the moment of chain scission. Presumably, the reaction follows the E1 mechanism involving the formation of an intermediate carbocation. The results show the possibility of using thermochemical degradation of biodegradable polyesters in solutions for obtaining their oligomeric bromo-substituted derivatives.

The colorful, unfading, and eco-friendly photonic crystal structural colors have attracted wide interest from textile researchers. However, to minimize the interference of incoherently scattered light, the preparation of the structural color fabric is still based on the black fabric, which seriously restricts the practical application of the structural colors in textile dyeing and finishing. This paper presented a straightforward strategy to construct structural colors on the fabrics by assembling polysulfide microspheres (PSMs) with self-absorbing light properties. The monodisperse PSMs were successfully synthesized through a polycondensation process between Na2S2 and 1,2,3-trichloropropane, whose particle size can be controlled by adjusting the volume ratio of ethanol-water. Four different structural colors were successfully obtained on white polyester fabric by varying the diameter of the PSMs arranged on the fabric surface in a face-centered cubic structure. Notably, the designed structural color fabrics had a low angle dependence, which was more meaningful for the textile color measuring and matching system.

Key Takeaways 1,2,3‐Trichloropropane, or TCP, is considered one of the most persistent organic groundwater contaminants and is linked to cancers and numerous damaging human health effects. The US Environmental Protection Agency has issued guidance on TCP and since it's not federally regulated, some states have established their own maximum contaminant levels. California's stringent TCP regulations and guidelines could serve as a blueprint for other states.

Recently, we found that Alcanivorax bacteria from various marine environments were capable of degrading halogenated alkanes. Genome sequencing of A. dieselolei B-5 revealed two putative haloalkane dehalogenase (HLD) genes, which were supposed to be involved in degradation of halogenated compounds. In this report, we confirm for the first time that the Alcanivorax bacterium encodes a truly functional HLD named DadB. An activity assay with 46 halogenated substrates indicated that DadB possesses broad substrate range and has the highest overall activity among the identified HLDs. DadB prefers brominated substrates; chlorinated alkenes; and the C2-C3 substrates, including the persistent pollutants of 1,2-dichloroethane, 1,2-dichloropropane and 1,2,3-trichloropropane. As DadB displays no detectable activity toward long-chain haloalkanes such as 1-chlorohexadecane and 1-chlorooctadecane, the degradation of them in A. dieselolei B-5 might be attributed to other enzymes. Kinetic constants were determined with 6 substrates. DadB has highest affinity and largest k cat/K m value toward 1,3-dibromopropane (K(m) = 0.82 mM, k(cat)/K(m) = 16.43 mM(-1) · s(-1)). DadB aggregates fast in the buffers with pH ≤ 7.0, while keeps stable in monomer form when pH ≥ 7.5. According to homology modeling, DadB has an open active cavity with a large access tunnel, which is supposed important for larger molecules as opposed to C2-C3 substrates. Combined with the results for other HLDs, we deduce that residue I247 plays an important role in substrate selection. These results suggest that DadB and its host, A. dieselolei B-5, are of potential use for biocatalysis and bioremediation applications.

California and Hawaii each have adopted a maximum contaminant level for 1,2,3‐trichloropropane (TCP) in drinking water, and other states have developed guidance for TCP; treatment of this emerging contaminant warrants careful consideration.