Overview of genotoxic carcinogens and non-genotoxic carcinogens. 1992

Y Hayashi
National Institute of Hygienic Sciences, Biological Safety Research Center, Tokyo, Japan.

It is known that carcinogens designated on the basis of longterm animal test results are extremely diverse in character, both in terms of potencies and the mechanism of action, which leads to complexity in their assessment for cancer risk to humans. The classification of carcin0ogens into two categories, namely, genotoxic and non-genotoxic varieties has been proposed to give a longical foundation on which cancer risk assessment can be reasonably based. The term "genotoxic carcinogen" indicates a chemical capable of producing cancer by directly altering the genetic material of target cells, while "non-genotoxic carcinogen" represents a chemical capable of producing cancer by some secondary mechanism not related to direct gene damage. This classification has contributed to the exclusion of various rodent-specific carcinogens from the group of chemicals with potential cancer risk to humans. However, the term, "nongenotoxic carcinogen" tends to give the mistaken impression that carcinogens shown to be negative for mutagenicity in a series of test systems might be harmless to humans. It should be realized that clear-cut criteria for this classification have not been established because of insufficiencies in the available information concerning mechanisms of action of non-genotoxic carcinogens. Future scientific advances leading to elucidation of the subcellular mechanisms of carcinogenesis are necessary for establishment of the unified, more realistic and mechanism-based approach to cancer risk estimation form exposure to chemicals.

UI MeSH Term Description Entries
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
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
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
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor

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