Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules
TLDR
Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens and there appears to be no requirement that they be electrophilic.Abstract:
Studies on a variety of chemical carcinogens have demonstrated that their ultimate reactive and carcinogenic forms are strong electrophiles. Some carcinogens, such as alkylating agents, are in their ultimate forms as administered, but most require metabolism to these active derivatives. The ultimate carcinogens react, usually non-enzymatically, with nucleophilic constituents in vivo. Of particular interest in regard to their possible importance in carcinogenesis have been the covalent interactions of these electrophilic reactants with cellular informational macromolecules, the DNAs, RNAs, and proteins. Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens. The nature of the carcinogen metabolite(s) involved in the promotion phase has not been determined, but there appears to be no requirement that they be electrophilic. The development of the concept of ultimate chemical carcinogens as strong electrophilic reactants is reviewed, especially with respect to the studies carried in the authors' laboratory.read more
Citations
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Journal ArticleDOI
Tobacco Smoke Carcinogens and Lung Cancer
TL;DR: By focusing in this review on several important carcinogens in tobacco smoke, the complexities in understanding tobacco-induced cancer can be reduced, and new approaches for lung cancer prevention can be envisioned.
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Biodegradation of polycyclic aromatic hydrocarbons
TL;DR: In this paper, the authors provide an outline of the microbial degradation of polycyclic aromatic hydrocarbons, including bacteria, fungi and algae, and the biochemical principles underlying the degradation.
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Cell proliferation in carcinogenesis
Samuel M. Cohen,Leon B. Ellwein +1 more
TL;DR: A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds.
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Biodegradation of polycyclic aromatic hydrocarbons
TL;DR: The intent of this review is to provide an outline of the microbial degradation of polycyclic aromatic hydrocarbons, a catabolically diverse microbial community, consisting of bacteria, fungi and algae, metabolizes aromatic compounds.
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Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: a review.
Weiling Xue,David Warshawsky +1 more
TL;DR: The DNA damages caused through the reactive metabolites of PAH/HAC are described involving the DNA covalent binding to form stable or depurinating adducts, the formation of apurinic sites, and the oxidative damage.
References
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Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid
James D. Watson,Francis Crick +1 more
TL;DR: The determination in 1953 of the structure of deoxyribonucleic acid (DNA), with its two entwined helices and paired organic bases, was a tour de force in X-ray crystallography and opened the way for a deeper understanding of perhaps the most important biological process.
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Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals
TL;DR: There is a high correlation between carcinogenicity and mutagenicity: 90% (156/174) of carcinogens are mutagenic in the test and despite the severe limitations inherent in defining non-carcinogenicity, few "non-Carcinogens" show any degree of mutageniability.
Journal Article
Pharmacological implications of microsomal enzyme induction
TL;DR: It is of considerable interest that certain inducers of liver microsomal enzymes have recently been used therapeutically for the treatment of hyperbilirubinemia in jaundiced children and for thetreatment of Cushing's syndrome.
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Metabolic activation of benzo(a)pyrene proceeds by a diol-epoxide
TL;DR: It is suggested that epoxides are the important reactive metabolites responsible for the biological effects of these carcinogens4.