Aflatoxins, Carcinogens in Food, as Etiological Factors in Human Malignant Neoplasias of the Lung

Lung cancer is a malignant neoplasm of the lung or bronchial cells and is one of the primary causes of mortality in men and is the third leading cause of death in women worldwide. Active and passive tobacco smoking are considered the main risk factors for the development of lung cancer, but aflatoxins have also been considered important etiological factors. Aflatoxins, which are fungal secondary metabolites produced primarily by Aspergillus spp., are chemically bis or tetra-hydrodifuran coumarins that contaminate foods (cereals, oilseeds, spices, dry fruits and dairy products). Aflatoxins are better recognized as hepatocarcinogens, but they can cause lung cancer via the formation of links to DNA and by the formation of AFB1-DNA adducts, which can remain in the DNA for years and cause mutations and eventually cancers. The ingestion of aflatoxin-contaminated foods is the most common way in which individuals are exposed to these carcinogens, but other routes of exposure include nasal aerosol inhalation of AFB1, which damages the lung. Alveolar macrophages possess specific oxidase activity for the epoxidation of AFB1. In the biotransformation of the lung by AFB1, AFB1 requires a catalyzed metabolic activation of cytochrome P450 (CYP), the levels of which are low in the lung, to exert its carcinogenic activity. AFB1 activation in the lung is achieved by prostaglandin H-synthetize, lipoxygenases, and CYP2A13 enzymes, the last of which catalyzes metabolic activation. CYP2A13 also plays a critical role in human lung carcinogenesis associated with inhalation exposure to AFB1 and is highly efficient in the activation of AFB1 in situ. Aflatoxins (AFB1 and AFG1) cause point mutations in K-Ras and H-Ras as well as in the p53 tumor suppressor gene, which can cause lung cancer. This article summarizes the known etiology of lung cancer with respect to the human food carcinogens AFB1 and AFG1, the molecular mechanisms of aflatoxins, and the known point mutations in the K-Ras, H-ras and p53 genes. This article also discusses a possible biocontrol (creosote bush or Larrea tridentata), the use of which is limited by its toxicity.