Smoke and urine

Lung damage due to smoking and exposure to smoke is generally detected only after the development of noticeable and serious symptoms. However, George Casale and collaborators from several U.S. universities and government organizations have been working together on a urine analysis method that could provide a much earlier determination of individual risk of lung cancer.

Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BP), which are present in cigarette and coal smoke, form electrophilic metabolites that bind and destabilize the N-glycosyl bond in DNA bases, thus depurinating them. Depurination of DNA is an important mechanism for carcinogenic mutation.The current study focused on detecting depurinated BP-adducted DNA bases, namely 7-(benzo[a]pyren-6-yl)adenine (BP-6-N7Ade) and 7-(benzo[a]pyren-6-yl)guanine (BP-6-N7Gua), in the urine of habitual cigarette smokers and women exposed to coal smoke (from communal kitchens in China), as an indication of cellular damage (Chem. Res. Toxicol. 2001, 14, 192–201).

Urine extracts were fractionated with HPLC and analyzed by mass spectrometry–capillary electrophoresis/laser-induced fluorescence. A number of individuals exposed to coal smoke or cigarettes had detectable levels of BP-6-N7Ade and/or BP-6-N7Gua in their urine, whereas all of those in the unexposed group did not. BP exposure levels from coal smoke were estimated to be as high as 23,000 ng/day (mostly BP-6-N7Gua), whereas BP-6-N7Ade exposure due to cigarette smoke intake was estimated at about 800 ng/day. Thus, these species seem to be useful for early detection of lung cancer risk.

It is interesting that several of the women exposed to coal smoke showed undetectably low levels of BP-6-N7Ade and BP-6-N7Gua.The researchers think this is more likely related to genetics rather than collection or detection methods. These individuals may have polymorphisms of cytochrome P-450 that hinder its normal role in activating the metabolism of PAHs into carcinogens. If the hypothesis is correct, then urine analysis for these compounds may be a means of testing for natural susceptibility to lung cancer.

The scientists are currently working on developing immunoaffinity/HPLC and gold biosensor chip protocols to ac commodate more in-depth studies of these BP-adducted bases and their associations with lung cancer and genetic variation.