Expression and variability of cytochrome P450 (CYP) 1A enzymes in 110 individual human lung samples and comparison with active smoking habits

Alemán. Background: The lung represents an important target tissue for the toxic effects of chemicals. Individual susceptibility towards lung toxicants might be due to interindividual variability of local metabolism in the lung. Interindividual variability of xenobiotic-metabolizing CYP enzymes can be genetically determined or influenced by environmental factors. Besides CYP2E1, whose pulmonary varaibility has been determined for the first time at the protein level, CYP1A enzymes were determined which also play a role in the activation of environmentally relevant chemicals. In order to determine variability of CYP1A enzymes 110 different individual lung samples, we used a previously established methodology to separate CYP1A1 and CYP1A2 and compared the results with data on smoking habits.Methods: Human lung tissue was obtained after informed consent and smoking habits were recorded. Microsomes were prepared and total protein content was determined. A Western Blotting procedure using a commercially available antibody was applied to quantify CYP1A1 and CYP1A2 simultaneously and to differentiate between the two enzymes.Results: CYP1A2 protein could be determined in all 110 individual lung samples, whereas CYP1A1 protein was detectable only in 41 of 110 samples. Comparison of these results with active smoking habits demonstrated, that CYP1A1 was only expressed in lung samples obtained from smokers. This finding is remarkable, because the patients had all stopped smoking preoperatively for at least four days. There were also lung samples from smokers, in which CYP1A1 protein could not be determined. The influence of the pattern of smoking cessation on CYP1A1 expression in smokers is currently under investigation.