Role of Dietary Antioxidants in Chemoprevention of Nitrosamines-Induced Carcinogenesis

Abstract

Cancer is a persistent public health challenge globally, and it is now one of the leading causes of mortality even in developed countries. Carcinogenesis is a complex multistep process of apparent molecular changes that eventually reprogram and transform normal cells into abnormal ones of uncontrolled cellular growth and division. Cancer-causing agents or carcinogens are those substances capable of initiating or promoting the process of carcinogenesis, essentially by alteration of the DNA – the key cellular genetic material. While carcinogens have varying mechanisms of action, a significant number of them exert their carcinogenicity through production of free radicals. High concentration of free radical in the body results in oxidative stress that leads to changes in the structure of DNA molecules, resulting in the mutation of protein/lipid structures, making of pro-inflammatory and anti-inflammatory cytokines, and excitation of stress-induced transcription factors, which concertedly play important roles in carcinogenesis. Many of the known chemical carcinogens fall among fairly well-defined chemical groups, like polycyclic aromatic hydrocarbons (PAHs), aromatic amines, and nitrosamides and nitrosamines. Nitrosamines are conspicuously excellent; several hundred have been tested, and most are potent experimental carcinogens, so their carcinogenicity has been widely studied. They exhibit their toxicity essentially by oxidative stress mechanism through generation of reactive oxygen species (ROS) methyl radicals, which methylate the nucleobases in nucleic acids leading to adenine thymine-guanine cytosine (AT-GC) transition mutations, resulting in tumors at both local and distant sites. Several studies have established that antioxidants have the ability to neutralize this effect and hence can prevent or attenuate the carcinogenic potentials of these amines. Interestingly, numerous diets are abundantly rich in these chemopreventive antioxidants, including lycopene (in tomatoes, watermelon, paw-paw, and grape seeds); flavonoids (in spinach and other green leafy vegetables); carotenoids (in carrots, mango, and other colorful fruits); phytoestrogens, mainly isoflavones like genistein and daidzein (in soya beans, fava beans, and peanut); isothiocyanates (in cruciferous vegetables such as cabbage, cauliflower, spring greens, and watercress); curcumin (in turmeric); selenium (in edible fish, lean meats and poultry, shellfish, eggs, beans); and vitamin E (in sunflower seed oil, almonds, and wheat germ oil). These phytonutrients, antioxidant vitamins and minerals, can potentiate antioxidant, anti-inflammatory, and immunological responses, including induction of apoptosis through increased expression and modulation of proapoptotic genes and inhibition of cell cycle progression. The established effects of this dietary antioxidant on nitrosamines imply, by extension, similar chemopreventive benefits against other carcinogens with oxidative stress as their underlying mechanism. Hence, the need for more advocacies on the use of medicinal natural substances from food plants as preventive and chemotherapeutic antioxidants for diseases such as cancer prevention and management can never be overemphasized.