Carcinogenicity of Organic Particulate Pollutants in Urban Air After Administration of Trace Quantities to Neonatal Mice

Epstein, Samuel S.; Joshi, Shree; Andrea, J.; Mantel, Nathan; Sawîckî, Eugene; Stanley, T. W.; Tabor, Elbert C.

doi:10.1038/2121305a0

Cited by 60 publications

(14 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several other laboratories also have demonstrated the utility of this bioassay to dissect the metabolic pathways responsible for converting chemical carcinogens to their genotoxic agents (26,27,3&32,34-39). Direct-acting chemical carcinogen classes that have been studied so far include polycyclic aromatic hydrocarbons (PAHs) (1,2,23,32,40), halogenated PAHs (38,41), nitrated PAHs (33), food pyrolysis products (heterocyclic amines) (25,26), complex environmental mixtures (42,43), nitrosamines (44), mycotoxins and other naturally occuring substances (29,45,46), vinyl compounds (29,46), azo dyes (30,47), aromatic amines (23,48), and allylarenes, such as estragole and safroles (49). The genotoxic mechanisms by which some of these compounds exert their tumorigenicity in the neonatal mouse also have been determined by employing the neonatal mouse for in v i m and/or in vivo studies.…”

Section: Highly Sensitive To Direct-mentioning

confidence: 99%

Neonatal Mouse Tumorigenicity Bioassay

Tungeln

et al. 1998

Drug Information J

View full text Add to dashboard Cite

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.

show abstract

Section: Highly Sensitive To Direct-mentioning

confidence: 99%

Neonatal Mouse Tumorigenicity Bioassay

Tungeln

et al. 1998

Drug Information J

View full text Add to dashboard Cite

show abstract

“…Various classes of genotoxic chemical carcinogens have been studied, including polycyclic aromatic hydrocarbons (PAHs) [9,10,[36][37][38], halogenated PAHs [33,39], nitrated PAHs [40][41][42], food pyrolysis products (heterocyclic amines) [30,31], complex environmental mixtures [43,44], nitrosamines [34], mycotoxins [34], vinyl compounds [34], azo dyes [34], aromatic amines [34], and allylarenes, including estragole and safroles [34].…”

Section: B Bioassay Of Genotoxic Chemical Carcinogensmentioning

confidence: 99%

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

Tungeln

Hammons

et al. 2000

Drug Metabolism Reviews

View full text Add to dashboard Cite

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.

show abstract

“…In addition, epidemiologists have been investigating the possible relationship between lung cancer and air pollution for about thirty years (Pike et al, 1975). Several investigators have previously produced animal tumors with extracts from air samples (Leiter and Shear, 1942;Epstein et al, 1966;Kotin et al, 1954). …”

Section: Lyon Francementioning

confidence: 99%

Mutagenicity, sister chromatid exchange inducibility andin vitro cell transforming ability of particulates from Athens air

et al. 1987

View full text Add to dashboard Cite

Airborne particulates were collected over a period of twelve months by the use of Hi-Vol samplers in the basin of Athens, Greece. N-Hexane extracts were tested in a battery of in vitro tests for their ability to induce mutation in bacteria as well as mutation, sister chromatid exchange and morphological transformation in cultured mammalian cells. Positive results were found for mutagenicity with Salmonella strain TA98 in the Ames assay, for sister chromatid exchange induction in CHO cells and for transformation in BALB/c 3T3 cells in culture. They also showed weak non-dose-related induction of ouabain resistance in BALB/c 3T3 cells. The contribution of oxidizing and nitrating agents found in the Athens atmosphere, together with sunlight UV irradiation in the formation of direct acting mutagens and potential carcinogens from ambient polycyclic aromatic hydrocarbons, is suggested.

show abstract

Carcinogenicity of Organic Particulate Pollutants in Urban Air After Administration of Trace Quantities to Neonatal Mice

Cited by 60 publications

References 7 publications

Neonatal Mouse Tumorigenicity Bioassay

Neonatal Mouse Tumorigenicity Bioassay

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

Mutagenicity, sister chromatid exchange inducibility andin vitro cell transforming ability of particulates from Athens air

Contact Info

Product

Resources

About