PubMed · 5467400
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1970-05-11. The DDT muddlement.. https://pubmed.ncbi.nlm.nih.gov/5467400/
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Unresolved DNA lesions trigger replication stress, forcing cancer cells to hijack DNA damage tolerance (DDT) networks, specifically translesion synthesis (TLS) and template switching, to sustain replication. While DDT prevents lethal fork collapse, error-prone TLS drives mutagenesis, tumor evolution, chemoresistance and radioresistance. Proliferating cell nuclear antigen post-translational modifications dynamically govern pathway selection. Cancer cells exploit this plasticity, creating actionable vulnerabilities such as postreplicative single-stranded DNA gaps. Emerging inhibitors targeting TLS polymerases, upstream regulators such as ubiquitin-specific peptidase 1 (USP1), and critical protein-protein interactions offer unprecedented opportunities for precision oncology. By integrating DDT inhibition with biomarkers such as homologous recombination deficiency and tumor mutational burden, we can drive synthetic lethality, sensitize tumors to genotoxic agents, suppress treatment-induced mutagenesis, and potentially enhance responses to immunotherapy.
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Disposal practices, accidental spills, leakages and local aerial deposition occurring in the past have led to local soil pollution in many cases. Especially in situations where people live on or nearby such locations this has created concern about possible adverse effects on human health. A stepped approach to the hazard assessment of polluted soil, as developed by a Task Force from the European Chemical Industry Ecology and Toxicology Centre (ECETOC), is described. In an early phase in the assessment process the potential exposure of humans is estimated. The Human Exposure to Soil Pollutants (HESP) model can be applied for this purpose. The model calculates the total exposure of adults and children resulting from pollutants present in soil, via 10 different exposure routes. The estimated exposure can be used to indicate the potential significant exposure routes and to carry out a preliminary hazard assessment. The model is also able to predict pollutant concentrations in soil which do not exceed accepted maximum exposure levels for humans in both standardised and site specific situations. The stepped approach is cost-effective and provides an objective basis for decisions and priority setting.