Related Experiment Video
Updated: Aug 6, 2026

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
Published on: September 25, 2017
Bacterial mutagenicity of some tobacco aromatic nitrogen bases and their mixtures
1Department of Environmental Health Sciences and Center for Occupational and Environmental Health, School of Public Health, University of California, 10833 Le Conte Avenue, Los Angeles 90095-1772, USA.
Abstract:
The first aim was to compare the genotoxicities of two tobacco-specific nitrosamines (TSNA), 4-(methylnitrosamino)-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) in two types of tests, the Salmonella reverse mutation assay (250-2000 microg per plate) and the Mutatox test (up to 1000 microg/ml) using dark mutant M-169 of Vibrio fischeri. The second aim was to assess the effects of single other tobacco chemicals and metabolites (nicotine (NIC), cotinine (COT), trans-3-hydroxycotinine (3HC), cotinine-N-oxide (CNO) and nicotine-N-oxide (NNO)) on the mutagenic responses at relative concentrations observed physiologically. The Salmonella strains were TA100, TA7004, TA7005, and TA7006, all showing missense backmutations that are characteristic of the TSNA. NNN was a direct mutagen to strains TA100, TA7004, and in the Mutatox test, and was not mutagenic in the presence of rat or hamster S9. NNK was mutagenic only in strain TA7004 with rat and hamster S9, but not in TA100, but was directly mutagenic in the Mutatox test. While all the other tobacco chemicals were not mutagenic alone to strains TA100 and TA7004 in the presence and absence of rat or hamster S9, the Mutatox test produced direct mutagenicity for COT, 3HC, and NNO, but not CNO. The latter was mutagenic in the Mutatox test with rat or hamster S9, but only rat S9 was effective for COT, NNO and 3HC. Inhibitory potentiations of NNN by NIC and COT were observed on strain TA7004, and by NIC on strain TA100. There were no interactions on NNK in the presence of S9 for strain TA7004 or TA100. In contrast, a complex inhibition and enhancement behavior occurred in the Mutatox test for each interaction, but no effects were observed for CNO on NNK without S9, and few for NIC on NNK with hamster S9. Compounds which showed no activity alone modulated the genotoxicity of two potent TSNAs in both types of tests.
Insights
This study compared the genotoxicity of tobacco-specific nitrosamines (TSNA) NNK and NNN using bacterial assays. Other tobacco chemicals modulated TSNA mutagenicity, indicating complex interactions in genotoxicity testing.
Area of Science:
- Toxicology
- Genetics
- Biochemistry
Background:
- Tobacco-specific nitrosamines (TSNA) are potent carcinogens found in tobacco products.
- Understanding the genotoxicity of TSNA and their interactions with other tobacco constituents is crucial for risk assessment.
Purpose of the Study:
- To compare the genotoxicities of NNK and NNN using Salmonella reverse mutation and Mutatox assays.
- To evaluate the effects of other tobacco chemicals and metabolites on TSNA mutagenicity.
Main Methods:
- Utilized Salmonella strains (TA100, TA7004, TA7005, TA7006) and Vibrio fischeri (Mutatox test).
- Assessed genotoxicity of NNK, NNN, nicotine (NIC), cotinine (COT), 3-hydroxycotinine (3HC), cotinine-N-oxide (CNO), and nicotine-N-oxide (NNO).
- Investigated interactions between TSNA and other tobacco chemicals with and without metabolic activation (S9).
Main Results:
- NNN was a direct mutagen in Salmonella TA100 and Mutatox tests.
- NNK was mutagenic in Salmonella TA7004 with S9 and directly mutagenic in the Mutatox test.
- COT, 3HC, and NNO showed direct mutagenicity in the Mutatox test.
- Other tobacco chemicals modulated TSNA genotoxicity, exhibiting complex interactions in both assays.
Conclusions:
- NNK and NNN exhibit distinct genotoxic profiles.
- Non-mutagenic tobacco compounds can influence the genotoxicity of potent TSNA.
- These findings highlight the importance of considering chemical interactions in tobacco genotoxicity assessment.
Related Concept Videos
Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
2° Amines to N-Nitrosamines: Reaction with NaNO2
Physical Properties of Amines
Mutagenicity and Carcinogenicity
Spontaneous and Induced Mutations
Other Unique Bacteria

