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• W2035764246 endingPage "1020" @default.
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• W2035764246 abstract "Although the necessity for metabolic activation of chemical carcinogens is well established, the critical target(s) for their action is not known. Many recent investigations have been based on the assumption that carcinogens act through somatic mutation and have focused on carcinogen‐nucleic acid interactions. Methods have been developed for detecting biological consequences of DNA damage caused by carcinogenic metabolites (for example, mutagenesis in prokaryotes or eukaryotes) or quantitating specific metabolite‐DNA adducts. Such methods have made it possible to elucidate probable ultimate carcinogenic forms and study cellular factors affecting carcinogen‐DNA interactions. It has been shown that numerous reactive metabolites of, for example, benzo[a] pyrene generated by microsomes are capable of binding to exogenous DNA in vitro, but in isolated organs or in cells and intact tissues most of these reactive forms are detoxified or otherwise “trapped” before they reach nuclear DNA. After binding, DNA repair mechanisms can also remove damaged bases. Binding of carcinogens to DNA affects the structure and function of the DNA, causing local denaturations and impaired transcription, but the significance of these findings in vivo is unclear. Because chemical carcinogenesis is a multistep process, a direct link between DNA binding and the final outcome, manifest cancer, is difficult to establish. Excellent correlations between mutagenesis, malignant transformation, and carcinogenesis may merely reflect the fact that the production of reactive intermediates is required for all these phenomena. Recent studies measuring “true” instead of “total” binding of carcinogens to DNA have yielded better correlations with mutagenesis and carcinogenesis. Nevertheless, much more must be known about the oncogenic process before it can be decided whether DNA is really the critical target for carcinogens and somatic mutation the initial step in the oncogenic process." @default.
• W2035764246 created "2016-06-24" @default.
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• W2035764246 date "1980-09-01" @default.
• W2035764246 modified "2023-10-18" @default.
• W2035764246 title "Binding of polycyclic aromatic hydrocarbons to DNA: Comparison with mutagenesis and tumorigenesis" @default.
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• W2035764246 doi "https://doi.org/10.1080/15287398009529923" @default.
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