Mechanisms of carcinogenesis: dose response. 1978

P J Gehring, and G E Blau

There is great controversy whether the carcinogenicity of chemicals is dose-dependent and whether a "threshold" dose exists below which cancer will not be induced by exposure. Evidence for dose-dependency exists and is believed to be accepted generally if extricated as it should be from the "threshold" concept. The "threshold" concept conflict is not likely to be resolved in the foreseeable future; proponents and opponents argue their case in a manner similar to those arguing religion. In this paper the various arguments are reviewed. Subsequently, a chemical process model for carcinogenesis is developed based on the generally accepted evidence that the carcinogenic activity of many chemicals can be related to electrophilic alkylation of DNA. Using this model, some incidence of cancer, albeit negligible, will be predicted regardless how low the dose. However, the model reveals that the incidence of cancer induced by real-life exposures is likely to be greatly overestimated by currently used stochastic statistical extrapolations. Even more important, modeling of the chemical processes involved in the fate of a carcinogenic chemical in the body reveals experimental approaches to elucidating the mechanism(s) of carcinogenesis and ultimately a more scientifically sound basis for assessing the hazard of low-level exposure to a chemical carcinogen.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
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
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000478 Alkylation The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. Alkylations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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