Molecular Epidemiology of Lung Cancer

Human Biomonitoring and Carcinogen Activation

Section: Section of Molecular Carcinogenesis

In our continuing investigations of the environmental factors influential in lung cancer aetiology, and the modulating effect of host factors, we are looking for explanations of the higher levels of DNA damage in the lungs of women smokers compared with male smokers. We investigated whether the role of oestrogen or the ERa receptor regulates the metabolic activation of polycyclic aromatic hydrocarbons in lung. Ovariectomy of female mice did not influence benzo[a]pyrene-DNA adduct formation in lung tissue, nor did transfection of a human lung cell line with ERα affect CYP1A1 activity. These data do not support the role of oestrogen or the ERα in regulating activation of polycyclic aromatic hydrocarbons in lung.

We have also found that resveratrol, a phytoalexin present in various plants and foods, inhibits the formation of benzo[a]pyrene–DNA adducts in cultured human lung cancer cells. Resveratrol may therefore be effective as a chemopreventive agent for lung cancer.

Studies have also indicated that smokers may be at increased risk of cancer of the anal epithelium. We have found that smokers have higher levels of DNA adducts in this tissue than non-smokers, indicating that tobacco carcinogens can reach this distal tissue and cause genetic damage in it. We are currently investigating tobacco-related DNA adducts in vulva.