Correlations between bioassay dose-level, mutagenicity to Salmonella, chemical structure and sites of carcinogenesis among 226 chemicals evaluated for carcinogenicity by the U.S. NTP. 1990

L P Brown, and J Ashby
ICI Central Toxicology Laboratory and Epidemiology Unit, Macclesfield, Cheshire, Great Britain.

Bioassay dose-level data for 226 chemicals unequivocally defined as carcinogens or non-carcinogens in mice and/or rats by the U.S. NTP have been standardized to gavage equivalent dose-levels according to a modification of the methods of Gold et al. Correlations by bioassay dose-level with chemical structure, mutagenicity to Salmonella, sites of carcinogenesis and extent of trans-species activity have been studied. The data obtained add further weight to the proposition that two classes of rodent carcinogen are present in the NTP database--genotoxic carcinogens that occur predominantly in the dose range 20-800 mg/kg and putative non-genotoxic carcinogens that are equally distributed over the dose range less than 20- greater than 3000 mg/kg. The latter carcinogens are characterized by the lack of structural alerts to DNA reactivity, the absence of mutagenicity to Salmonella, an inability to induce tumours in 8 reference tissues and a strong tendency to be tissue and species-specific in their activity. Where comparisons can be made, the present findings for the NTP carcinogens and non-carcinogens are consistent with the recent observations by Gold et al. for a larger group of carcinogens.

UI MeSH Term Description Entries
D008297 Male Males
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
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
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
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
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
D005260 Female Females
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
D012475 Salmonella A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility.
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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