Mutagenic activity of three isomeric N-nitroso-N-methylaminopyridines towards Escherichia coli K-12 in in vitro and animal-mediated assays.

doi:10.1093/CARCIN/3.4.415

Paper

Mutagenic activity of three isomeric N-nitroso-N-methylaminopyridines towards Escherichia coli K-12 in in vitro and animal-mediated assays.

Published 1982 · P. Kerklaan, S. Bouter, G. Mohn

Carcinogenesis

Q1 SJR score

9

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0

Influential Citations

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Abstract

Three isomeric nitrosomethylaminopyridines (2-NMPY, 3-NMPY, and 4-NMPY), of which only the 2-isomer exerts significant carcinogenic activity in rats, were tested in vitro and in the host-mediated assay for their activity to induce gene mutations in E. coli K-12 strain 343/113. Two related carcinogenic nitrosamines were also tested, namely, nitrosodimethylamine (NDMA) and nitrosomethylaniline (NMA). The in vitro mutagenicity tests were performed either without or in the presence of various fractions (S-9, microsomes, S-100) of rodent liver homogenates. The in vivo mutagenicity was determined in host-mediated assays, in which the indicator E. coli cells were recovered for the liver of treated animals. In experiments involving the S-9 liver fraction, only 2-NMPY among the nitrosomethylaminopyridines exerted a slight mutagenic effect. The low mutagenicity of this isomer, and the non-mutagenicity of the remaining 3- and 4-isomer could be partly explained in experiments involving microsomes and the S-100 fraction of rodent liver: 2-NMPY and 4-NMPY were activated to mutagenic factors by microsomes, but their mutagenic effect was completely abolished when S-100 was added. 3-NMPY, on the other hand, was directly mutagenic for E. coli but, again, its mutagenic potential was abolished when S-100 liver fraction was added to the incubation mixtures. NDMA was activated to mutagenic factors with both microsomes and S-9 fractions, whereas NMA could not be shown as mutagenically active under any of the present experimental conditions. It could be shown that the deactivating effect of the S-100 fraction was of nonenzymatic nature, and probably was due to the presence of thiol-containing "scavenger" molecules in this fraction. In the host-mediated assays, only the 2-isomer among the three exerted a mutagenic affect. The present results indicate that the three isomers investigated here are mutagenic either directly (3-NMPY) or upon microsomal activation (2-NMPY and 4-NMPY). The non-carcinogenicity of 3-NMPY and 4-NMPY, and the non-mutagenicity of these compounds in host-mediated assays, is probably the result of very efficient deactivation by cytosolic (thiol-group-containing?)factors.

In Vitro Study

Study Snapshot

The three isomers of nitrosomethylaminopyridines are mutagenic towards Escherichia coli K-12, with only 2-NMPY showing significant carcinogenic activity in rats, and their non-carcinogenicity and non-mutagenicity in host-mediated assays

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Mutagenic activity of three isomeric N-nitroso-N-methylaminopyridines towards Escherichia coli K-12 in in vitro and animal-mediated assays.

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References

Citations

Ames mutagenicity of 15 aryl, benzyl, and aliphatic ring N-nitrosamines.

The Ames mutagenicity test effectively identifies carcinogenic potential in nitrosamines, with aliphatic ring compounds showing a negative relationship between mutagenicity strength and carcinogenic potential.

Applicability of a Host-mediated In Vivo/In Vitro Model in Screening for the Carcinogenic Potential of Chemicals

A host-mediated in vivo/in vitro assay effectively screens for carcinogenic potential of chemicals, offering advantages over traditional in vivo and in vitro tests.

Methodologies for the determination of various genetic effects in permeable strains of E. coli K-12 differing in DNA repair capacity. Quantification of DNA adduct formation, experiments with organ homogenates and hepatocytes, and animal-mediated assays.

Quantitative tests in vitro and host-mediated assays can help assess genotoxic properties of chemicals for which long-term in-vivo data is not yet available.

Activation of nitrosamines and other carcinogens by mouse-liver S9, mouse hepatocytes and in the host-mediated assay produces different mutagenic responses in Salmonella TA1535.

Mouse hepatocytes and mouse-liver homogenates have limited capacity to activate carcinogens, but both have a marginal potential to activate low amounts of these compounds compared to host-mediated assays.

Use of differential DNA-repair host mediated assays to investigate the biotransformation of xenobiotics in Drosophila melanogaster. I. Genotoxic effects of nitrosamines.

Nitrosamines show dose-dependent genotoxic effects in Drosophila melanogaster, with carcinogenic compounds showing the strongest response and phenobarbital feeding increasing DNA damage potencies.