Dose-response relationship for chemical carcinogenesis by genotoxic agents. 1991

W K Lutz
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.

Formation and repair of DNA adducts from genotoxic carcinogens is expected to be proportional to dose as long as the rates of the enzymatic and non-enzymatic activation and inactivation reactions are all proportional to the substrate concentration. Deviations from linearity are expected in situations of induced and saturated kinetics. A sublinear shape of the dose-response curve is always expected at toxic dose levels when regenerative hyperplasia accelerates the fixation and accumulation of mutations resulting from the DNA adducts. In a heterogeneous population, however, a nonlinear dose-response curve is linearized when genetic and life-style factors result in individual variability in the rates of the activation and inactivation pathways. Finally, in the light of the endogenous and therefore partly unavoidable nature of genetic damage, it is proposed that the cancer risk from exposure to an exogenous carcinogen should be expressed as a reduction of tumor-free life span rather than in absolute terms of additional cases.

UI MeSH Term Description Entries
D009381 Neoplasms, Radiation-Induced Tumors, cancer or other neoplasms produced by exposure to ionizing or non-ionizing radiation. Radiation-Induced Cancer,Cancer, Radiation-Induced,Radiation-Induced Neoplasms,Cancer, Radiation Induced,Cancers, Radiation-Induced,Neoplasm, Radiation-Induced,Neoplasms, Radiation Induced,Radiation Induced Cancer,Radiation Induced Neoplasms,Radiation-Induced Cancers,Radiation-Induced Neoplasm
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016296 Mutagenesis Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS. Mutageneses

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