**13. Impact of new technologies or analytical techniques and biomedical engineering**

Recent advances in molecular methodologies are phenomenal, and they increasingly are being applied to understanding the interaction of chemical carcinogens with cellular constituents and metabolism. Cloning of DNA has facilitated the identification of specific genes mutated in human cancers. Chemical methods, including mass spectrometry, allow us to measure carcinogen alteration with unprecedented sensitivity and specificity, particularly the ultra high performance liquid chromatography (UHPLC) coupled to MS. Mass spectrometry is being coupled with many other site-specific techniques to study mutagenesis; to define how specific alterations in DNA produce cognate mutations. Sequencing of the human genome and the identification of DNA restriction enzymes opens up the field of molecular epidemiology, focusing in part on individual susceptibility to carcinogens.

A very useful technique in cancer studies is the single cell protein electrophoresis (COMET ASSAY). This assay is the only direct method for the detection of DNA damage in cells. It is used in cancer research, in genotoxicity studies on environmental mutagens, and for screening compounds for cancer therapeutics.

DNA microarray technology is a powerful tool that allows the activity of several genes to be monitored simultaneously. DNA microarray has been especially useful for detecting genes that respond to a specific chemical or physical signal in the same way. A DNA microarray or DNA chip consists of a solid surface, usually glass, to which DNA fragments are attached. The copies of each kind of fragments are attached to the glass surface at a specific site to regular pattern or array. DNA fragments attached to the chip act as probes that can hybridize with complimentary DNA or RNA molecules (targets) in solution. DNA microarray technology has been used to study a wide variety of gene expression problems such as tissue specific, cell cycle specific, and tumor- specific gene activation and repression. Once a similar pattern expression profile has been established for a group of genes, it seems reasonable to assume that the profile is at least partly caused by similar transcription regions. Therefore, if information is available about a regulatory region in one gene within this group, it may provide clues to the regulatory regions of other members of the group as well as to the protein factors that activate or inhibit gene expression. The initial stimulus may be a given carcinogen. Array technology facilitates analysis of carcinogen-induced alterations in the expression of both protein coding and noncoding genes. These are all areas where biomedical engineering is expected to play a pivotal role in risk identification and early detection. On the horizon are techniques that can measure single molecules of carcinogens in cells, random mutations in individual cells, analysis of the dynamics of how molecules exist and work, and bioinformatics and genetic maps to delineate complex interacting functional pathways in cells. Underlying this progress in understanding chemical carcinogenesis is a cascade of advances in molecular biology that makes it feasible to quantify DNA damage by chemical agents, mutations, and changes in gene expression.

This calls for very intimate collaboration between biotechnology and biomedical engineering, a partnership that promises to be very rewarding in the fight against chemical carcinogenesis. Determining the structure of DNA, DNA sequencing, and the PCR revolutionized cell biology, including carcinogenesis. Advances in detection of DNA damage, including postlabeling of DNA (Randerath et al, 1981), immunoassays (Poirier et al, 1977) and mass spectrometry as earlier discussed (Singh and Farmer, 2006) have allowed the detection of a single altered base in 109 nucleotides using human nuclear DNA. This technology can be extended to analyze DNA or RNA in a single cell (Klein, 2005). Advances in cell biology, including array technology (Schena et al, 1995) and proteomics (Anderson et al, 1984; Aebersold et al, 1987), make it feasible to assess global changes in RNA and protein expression during carcinogenesis. Together, these technologies underlie systems biology, making it increasingly feasible to map biochemical pathways in cancer cells from DNA, to RNA, to proteins, to function. This again calls for greater involvement of the biomedical engineering field.

The ultimate application of techniques of biomedical engineering in the field of chemical carcinogenesis holds great promise, but faces several formidable challenges requiring ingenuity in matching technology with a social obligation to ensure that those most affected can afford its dividend to combat the menace of chemical carcinogenesis. This calls for sensitive methods for the early detection. The complex interplay among these and the great promise they hold for human health, particularly in the rapidly industrializing developing countries has not been adequately addressed. This contribution largely sees this as needing to be addressed- carcinogenesis, integrating chemical exposure, nutritional; mainly micronutrient modulation and the yawning gap biomedical engineering should fill in non-invasive applications. Although the field of biomedical engineering as regards cancer studies is still relatively in its early stages and will be a long-term effort and the magnitude of the task far greater than the physical resources and intellectual capacity currently available, the challenge is to focus on sensitive, specific or selective, cost effective and efficient techniques with dereliction for resource poor rapidly industrializing developing countries that appear to bear a greater brunt of the increasing chemical exposure and attendant carcinogenic risk.

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