Tests for Carcinogenesis Using Newborn Mice: 1,2-Benzanthracene 2-Naphthylamine, 2-Naphthylhydroxylamine and Ethyl Methane Sulphonate

Roe, F. J. C.; Mitchley, B. C. V.; Walters, Margaret

doi:10.1038/bjc.1963.36

Cited by 29 publications

(7 citation statements)

References 13 publications

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“…EMS and MMS are closely related analogs which differ with respect to carcinogenic potential as deter mined by tumor induction [4,5]. MMS is a highly car cinogenic mutagen, while EMS is a rare or weakly car cinogenic mutagen.…”

Section: Discussionmentioning

confidence: 99%

“…Several known and suspected po tent carcinogens, including methyl methanesulfonate (MMS), markedly inhibited the induction of interferon by Newcastle disease virus (NDV) in mouse embryo fibroblasts. The rarely or weakly carcinogenic analog of MMS, ethyl methanesulfonate (EMS) [4,5] had little or no effect on the induction of interferon by NDV. Therefore, the new data suggest that interferon induc tion is inhibited by pretreatment of cell cultures with an extended group of potent carcinogens.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Carcinogens and Analogs on Interferon Induction

Barnes

Streips

Sonnenfeld³

1981

Oncology

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Pretreatment of mouse embryo fibroblasts with several chemicals, including 7,12-dimethylbenz-(α)-anthracene, 2-aminofluorene, aflatoxin B₁, benzo-(α)-pyrene, styrene oxide, and the No. 4 fraction of tobacco smoke condensate, resulted in severely reduced production of interferon when the cells were challenged with Newcastle disease virus. All of the above chemicals are proven or strongly suggested carcinogens. When the analogs methyl methanesulfonate, a potent carcinogen, and ethyl methanesulfonate, a weak carcinogen, were applied to cells, interferon induction was only inhibited by the methyl methanesulfonate. Therefore, carcinogens may directly inhibit the induction of interferon by Newcastle disease virus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Carcinogens and Analogs on Interferon Induction

Barnes

Streips

Sonnenfeld³

1981

Oncology

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“…Following these initial results, extensive studies were conducted to determine the tumor susceptibility of neonatal mice to different classes of chemicals. A number of different strains and dosing regimens were employed [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. These experiments were conducted both to explore the parameters for using neonatal mice for routine testing of chemical carcinogens and to determine the factors that can affect differences in tumor susceptibility.…”

Section: A Historical Background and General Considerationsmentioning

confidence: 99%

Metabolic Activation Capacity of Neonatal Mice in Relation to the Neonatal Mouse Tumorigenicity Bioassay

Tungeln

Hammons

et al. 2000

Drug Metabolism Reviews

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The neonatal mouse tumorigenicity bioassay is a well-developed animal model that has recently been recommended as an alternative tumorigenicity bioassay by the International Conference on Harmonization (ICH) for Technical Requirements for the Registration of Pharmaceuticals for Human Use. There are sufficient data to conclude that this animal model is highly sensitive to genotoxic chemical carcinogens that exert their tumorigenicity through mechanisms involving the formation of covalently bound exogenous DNA adducts that lead to mutation. On the other hand, it is not sensitive to chemical carcinogens that exert tumorigenicity through a secondary mechanism. The metabolizing enzymes present in the neonatal mouse, particularly the cytochromes P450, are critical factors in determining the tumorigenic potency of a chemical tested in this bioassay. However, compared to the metabolizing enzymes of the adult mouse and rat, the study of the metabolizing enzymes in neonatal mouse tissues has been relatively limited.

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“…A subsequent study reported in 1961 by the same group (2) indicated that Swiss newborn mice receiving benzo[a]pyrene, 3-methylcholanthrene, dibenz[a,h]anthracene, or urethane (ethyl carbamate) developed malignant lymphoma and pulmonary tumors. Throughout the early to mid 1960s, the susceptibility of neonatal mice of different strains and dosing regimens to a variety of chemicals of various structures was widely studied (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). In general, it was shown that different strains of neonatal mice were highly susceptible to chemicallyinduced tumor formation.…”

mentioning

confidence: 99%

Neonatal Mouse Tumorigenicity Bioassay

Tungeln

et al. 1998

Drug Information J

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The International Conference on Harmonisation (ICH) has suggested the use of the newborn mouse bioassay as an alternative tumorigenicity assay. There are sufficient data to conclude that this animal model is highly sensitive to chemical carcinogens that exert their action through mechanisms involving the formation of covalently bound DNA adducts (exogenous d u c t s ) of the administered compound and the processing of these adducts to mutations.Mechanistic studies, including metabolism, DNA adduct formation, and ras-oncogene activation, presented in this paper aid in the interpretation of tumor experiments. By comparison, the data thus far obtained suggest that this bioassay is very likely insensitive to some indirect-acting chemical carcinogens. Ongoing studies are focused on the sensitivity of this bioassay to indirect-acting carcinogens that are believed to exert their tumorigenicity through secondary mechanisms, including: 1. induction of lipid peroxidation and increases in endogenous DNA adducts, 2. endocrine disruption, and 3. induction of peroxisome proliferation. A systematic approach to validate the neonatal mouse tumorigenicity bioassay as a part of a risk identification procedure is proposed. This approach combines the tumorigenicity bioassay with several simple and convenient supportive mechanistic experiments of study so that direct-acting chemical carcinogens, indirectacting carcinogens, and noncarcinogens can be distinguished.

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Tests for Carcinogenesis Using Newborn Mice: 1,2-Benzanthracene 2-Naphthylamine, 2-Naphthylhydroxylamine and Ethyl Methane Sulphonate

Cited by 29 publications

References 13 publications

Effect of Carcinogens and Analogs on Interferon Induction

Effect of Carcinogens and Analogs on Interferon Induction

Metabolic Activation Capacity of Neonatal Mice in Relation to the Neonatal Mouse Tumorigenicity Bioassay

Neonatal Mouse Tumorigenicity Bioassay

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