Monitoring exposure to tobacco-specific nitrosamines
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Two kinds of disease-causing chemicals are found in tobacco smoke. One kind is called Polynuclear Aromatic Hydrocarbons (PAH). PAH is usually associated with products of burning (so-called "tar") and is not unique to tobacco. The other kind is called Tobacco-Specific NitrosAmines (TSNA). TSNA occurs in unburned tobacco and enters the body when hot smoke passes through a cigarette.
 
 
 
 
 
 PAH is associated with one form of lung cancer, and TSNA is associated with another. The form that is caused by PAH used to be the most common lung cancer that was seen. Nowadays, however, both forms are equally common. Could this change be a result of changes in smoking habits? Could exposure to TSNA increase a result of the measures taken (filters or low-tar cigarettes, for example, or "tobacco-heating" cigarettes) to reduce PAH?
 
 
 
 
 
 To answer this kind of question, we need to find some way to measure TSNA exposure. One way would be to develop a blood test to tell how much TSNA a person has taken in. Because we don't have many ideas how to do this, a fundamental set of experiments is proposed, to see if the most important known TSNA (known as the N-Nitroso Ketone, or NNK) sticks to a type of blood cell known as a platelet. The outside of cells like platelets is called the plasma membrane. Each type of cell has distinctive, natural markers on the outside surface of its plasma membrane. It seems plausible that one of the markers characteristic of platelets may become tagged by NNK. If this is the case, then it should be possible to develop sensitive techniques to measure how much NNK has stuck to the outside of platelets.
 
 
 
 
 
 We don't know yet whether NNK sticks to the outside of any cell. To find out, the first experiments need to explore ways to detect small amounts of chemicals that react with the natural cell-surface markers. This project examines how easily natural cell-surface markers on platelets can be tagged by radioactive chemicals. This will tell how effectively the measurement method works, because it will tell if we can separate the sort of marker that gets tagged from the many other markers that should not be tagged. This work is proceeding in 4 stages:
 
 
 
 
 
 (1) Take a methodology that we have recently developed for water-soluble enzymes and adapt it to look for proteins that occur on the surface of a cell. The target cells will be blood platelets, which are responsible for clotting (and are also involved in heart disease);
 
 (2) Use this methodology to examine if platelets attach radiolabeled NNK in such a way that it cannot be washed off;
 
 (3) Separate the proteins and use a newly developed, ultrasensitive technique (called AMS) to identify those that are tagged;
 
 (4) Clip the tagged proteins into smaller pieces, so that they can be identified in future.
 
 With the data from this study one can then decide whether it will be possible to develop a test (called an immunoassay) to measure the extent to which platelet surfaces react with natural NNK.