NNALs: Measuring Exposure to a Tobacco-Specific Carcinogen

Key messages

• 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific lung carcinogen found in tobacco products and tobacco smoke.
• 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is produced from the breakdown of NNK in the body. It is an excellent biomarker of exposure to tobacco products and to the tobacco specific carcinogen NNK.

Background

Tobacco products contain many naturally occurring chemicals, including those known to cause, initiate, or promote cancer (Footnote 3  One of these carcinogens--NNK (chemical name: 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone) has been linked specifically to the development of lung cancer in humans.^{Footnote 4}

• Tobacco-specific N-nitrosamines (TSNAs) found in tobacco products and tobacco smoke
  • N-nitrosonornicotine (NNN)
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
  • N-nitrosoanatabine (NAT)
  • N-nitrosoanabasine (NAB)

The metabolism of NNK

Both unburnt tobacco products and tobacco smoke contain NNK. It is formed from the nicotine in tobacco during the curing process.3 When a person uses a tobacco product or is exposed to tobacco smoke, NNK is absorbed into the body and metabolized--mostly by the liver--to produce 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), NNAL-N-Glucuronide and NNAL-O-Glucuronide. These metabolites of NNK are known collectively as total NNAL or, simply, NNALs.^{Footnote 1} 

NNALs as biomarkers of exposure to tobacco products

NNALs are useful biomarkers for measuring exposure to tobacco products and to the tobacco-specific lung carcinogen NNK. NNALs are excreted in urine, and can be detected for several weeks following exposure which helps them to be detected and measured. NNALs have allowed researchers to distinguish between smokers, non-smokers, consumers of smokeless tobacco products, and people who are exposed to second-hand smoke.^{Footnote 2} 

NNALs are some of the best biomarkers of exposure to tobacco. Like cotinine, NNALs are specific to tobacco products and tobacco smoke and cannot be produced from other sources, and therefore provide reliable results. However, NNALs remain much longer in the body than cotinine, so researchers can study individual tobacco use patterns. NNALs can also be used to study the exposure of individuals to the carcinogenic chemical NNK, which cannot be done using cotinine.

The future

NNALs are some of the 91 chemicals measured by the Canadian Health Measure Survey (CHMS)--a survey done by Statistics Canada to examine the exposure of Canadians to a variety of environmental chemicals. By measuring tobacco-specific biomarkers of exposure such as NNALs, researchers can better study smoking prevalence and the exposure of Canadians to tobacco products and tobacco smoke.

Glossary of Terms

Metabolism

The whole range of biochemical processes that occur within an organism. Metabolism consists of build-up and breakdown of substances.

Metabolite

The substance, or product, resulting from a metabolic process.

Specific

Related in application, or effect, to a particular chemical, structure, or process.

Toxicant

Artificially produced poison or poisonous substance.

Uptake

Absorption and incorporation of a substance by live tissue.

Footnotes