**7. Mechanism of oxidative stress and DNA damage due to micronutrient deficiency**

Micronutrients are referred to as nutrients required in very small amounts that do not have calorific values but are extremely important for the maintenance of health. They comprise the vitamins and trace elements that regulate vital metabolic and molecular pathways and

If the induced mutations occur at one or a relatively few critical sites on the DNA, then the cells may be converted from a "normal" to a preneoplastic state. Chemically-induced mutations are not limited to critical genes, different pretumor cells may demonstrate a variety of different growth potentials due to the range of altered " non-critical" genes, thus enabling those cells with most favourable properties to transform most rapidly to clinically apparent tumours. Alternatively, the carcinogens may act indirectly through the formation of reactive oxygen species or nitrogen radicals, some types of which are also highly reactive with macromolecules such as DNA. The process of raised cellular proliferation is also multifactorial in its genesis. It may arise from, for instance, direct hormone-like stimulation of specific cell types, from perturbation of tissue processes that lead to a balance between cell proliferation and cell death (apoptosis), it may alternatively arise from massive cell-killing or cytotoxicity followed by proliferative regeneration to maintain the physiological functioning of the affected tissues. A yet further way by which excess, tumor-inducing cellular division may be induced is that exhibited by the urinary bladder. Oyasu and his colleagues (1981) and in his subsequent studies (1995) showed by using heterotopical transplant rat bladder technique that urine by itself, but not water can induce proliferation.

It was however conceived that urine contained epithelial growth factors that stimulate cell division and that such factors would penetrate the epithelium should it be injured by the presence of a foreign agent in the bladder. A fourth type of mechanism of carcinogenesis may arise from the ability of the agent to form a complex with a specific protein. This complex (ligand-protein) may have the property of altering the expression of specific and important region in the DNA. There is the emerging but incompletely understood involvement of epigenetics; alteration in the genetic processes not involving DNA base sequence. Many epimutagens have already been identified and a number of existing

Cancers caused by environmental agents frequently occur in tissues with the greatest surface of exposure to the agents: lung, gastrointestinal tract, and skin. Recently, the study of chemical carcinogenesis has merged with studies on the molecular changes in cancer cells, thus generating biological markers to assess altered metabolic pathways and providing new targets for therapy. Although these are exciting areas, they may be peripheral to attacking the primary causes of the most common human cancers. As more and more mutations are catalogued in cancer cells and more and more changes in transcription regulation, it becomes increasingly apparent that we need to understand what generates these changes. The fact that chemicals cause random changes in our genome immediately implies that our efforts need to be directed to quantifying these changes, reducing exposure, and developing approaches to chemoprevention (Extensively reviewed by Pereira, 1997).

**7. Mechanism of oxidative stress and DNA damage due to micronutrient** 

Micronutrients are referred to as nutrients required in very small amounts that do not have calorific values but are extremely important for the maintenance of health. They comprise the vitamins and trace elements that regulate vital metabolic and molecular pathways and

The mechanism by which this happens is not quite clear.

**6. The environment and cancer** 

**deficiency** 

chemicals such as cadmium are also known to act through this pathway.

processes. Some of them play very vital roles in DNA and RNA metabolism either as coenzymes or cofactors involved in their metabolism or as components of systems intimately interacting with these molecular regulators. The micronutrients are basically supplied in the diet or may be taken as supplements. Very few of them are synthesized endogenously enough to meet physiological requirements hence they are mostly essential.

Based on public data emanating from the Healthy People 2010 Project, it has been estimated that about 80% of colon and prostate cancers, may be influenced by diet, nutrition, and life style. It has been proposed that DNA damage induced by dietary micronutrient deficiency accounts for about 33% of preventable cancers (Ames, 2001; Ames and Wakimoto, 2002). Owing to the fact that micronutrient deficiencies can induce DNA damage in a manner similar to those induced by ionizing radiation and reactive oxygen species (ROS), it has been suggested that oxidative stress and the associated DNA breaks are critical targets for nutritional control of carcinogenesis (Cheng, 2009) and perhaps a marker for early detection. When DNA lesions are left unrepaired they can promote accumulation of mutations that facilitate the process of carcinogenesis. Micronutrients may act directly on the genome to prevent mutations, or indirectly as enzyme cofactors in cellular processes that modulate transformation (Hanahan and Weinberg, 2000; Sjoblom et al., 2006). By yet incompletely defined mechanisms, micronutrients at levels higher than nutritional requirements may also activate DNA damage response or senescence, which are processes that are recognised to eliminate cancer cells or limit the progression of precancerous cells (Gorgoulis et al., 2005; Bartkova et al., 2005, 2006). The essential microminerals copper, iron, selenium and zinc play important roles in genome stability. In particular, these microminerals have significant impact on oxidative DNA damage and the corresponding repair pathways.

Micronutrient intakes below recommended levels are known to be unusually widespread in poor countries, though also some segments of the population in economically advanced nations such as the United States, especially among the poor, children, adolescents (Anetor, 2009; Ames, 2010). It has been hypothesised that two of the many insidious but measurable consequences of moderate micronutrient inadequacy are increased DNA damage (precursor of cancer) and mitochondria decay which can cause mutagenic oxidant release also involved in future carcinogenesis. Studies indicate that sensitive assays targeted at these end points have a high probability of detecting changes in individuals with micronutrient deficiencies(Ames, 2010) This again appears instructive to scientists and technologists in the biomedical engineering field.
