China 
Africa 
Explore chapters and articles related to this topic
Measurement of Exposure and Dose
Published in Samuel C. Morris, Cancer Risk Assessment, 2020
Especially exciting opportunities for biomarkers of exposure are found in DNA adducts. The active forms of many chemical carcinogens are metabolites which bind to cellular macromolecules, including nucleic acids and proteins; the product of these bindings are called adducts. The formation of DNA adducts are thought by many to be cancer-initiating events (Wogan and Tannenbaum, 1987). What better index of the biologically effective dose than the actual dose causing the initiating event itself. As discussed earlier (Chap. 2), in addition to initiation, the progression step in carcinogenesis may also require a DNA-damaging event. Thus, DNA adducts may be indicators of exposure affecting both early and late steps in cancer development (Harris, 1985). Much work has been done to build an understanding of the relationship between exposure or, in experimental animals, administered dose, and the levels of DNA adducts. A linear relationship is often, but not always, found (Perera, 1987; Belinsky et al., 1987; Adriaenssens et al., 1983; Dunn, 1983). Pharmacokinetics, discussed in a later chapter, rules this relationship.
Determining DNA Adducts by Electrophore Labeling-GC
Published in Frederick C. Kopfler, Gunther F. Craun, Environmental Epidemiology, 2019
Electrophore labeling-GC-MS methodology can greatly advance the determination of DNA adducts. It is ultrasensitive, definitive, avoids handling of radioisotopes, can potentially determine several adducts simultaneously, utilizes internal standards, and can discover and elucidate the structures of unknown adducts. Alternate immunoassay and 32p-post labeling methodologies, although successful for determining DNA adducts, do not provide some of these advantages. For example, there is little structural information in the autoradiographic spots that are the final outcome of determining DNA adducts by 32p post labeling. Immunoassays tend to require a separate, high-affinity and high-specificity antibody for each adduct. Such an antibody may not always be available, or may require considerable time to develop, whereas electrophore-GC-MS methodology potentially can move quickly onto new adducts once the general methodology has been developed.
Molecular Fluorescence and Phosphorescence
Published in Grinberg Nelu, Rodriguez Sonia, Ewing’s Analytical Instrumentation Handbook, Fourth Edition, 2019
Ricardo Q. Aucelio, Sarzamin Khan, Andrea R. da Silva, Fernando M. Lanças, Emanuel Carrilho
The use of laser-induced fluorescence in capillary electrophoresis (CE) is very advantageous because the high intense excitation beam can be very efficiently focused on a small capillary detection volume. This is of great advantage considering the small volume of samples employed in these cases. Detection as low as 10−20 mol in a nanoliter volume has been accomplished (Guthrie et al., 1984; Gassman et al., 1985; Lee et al., 1993). CE has actually been one of the best approaches to accomplish SMD and the probing of single cells and DNA adducts (Wang et al., 2002). The combination of multicolor fluorescence detection and CE helped to finish the s equencing of the human genome ahead of schedule, taking advantage of RET dyes, enzymes, and proper optical schemes (Franca et al., 2002). Several fluorescence detection approaches have been successfully applied for the detection of DNA adducts (Schmitz et al., 2002; Formenton-Catai and Carrilho, 2003). DNA sequencing has benefited from improvements in the association of fluorescence detection and CE that lead to robustness and reliability (Marziali and Akeson, 2001;Landers, 2002). The use of the micellar electrokinetic chromatography approach, accomplished by using a surfactant above CMC in the background electrolyte, has been used to improve detection of fluorophores (Meng et al., 2014) and the indirect detection by phosphorescence quenching (Castro-Puyana et al., 2011).
Pesticide exposure and genotoxic effects as measured by DNA damage and human monitoring biomarkers
Published in International Journal of Environmental Health Research, 2021
Jones A. Kapeleka, Elingarami Sauli, Patrick A. Ndakidemi
Exposure to pesticides exhibits increased level of DNA damage even if no detectable amounts of pesticides are seen in the blood serum because pesticides exhibit toxicity by binding specific areas in the DNA (Kasiotis et al. 2012). The mutagenic and carcinogenic nature of these toxic chemicals is explained by the formation of DNA adducts (Rusiecki et al. 2017). Moreover, pesticide exposure induces oxidative stress by depleting intracellular glutathione and increasing reactive oxygen species (ROS) production as a result of the metabolism process of pesticides. This produces more toxic metabolites harmful to cells (Sabarwal et al. 2018). Metabolic activities of pesticides within human bodies are considered an important underlying cause of mutations leading to cancer (Singh et al. 2011; Hernandez et al. 2013; Gómez‐Martín et al. 2015).
Key characteristics of 86 agents known to cause cancer in humans
Published in Journal of Toxicology and Environmental Health, Part B, 2019
Daniel Krewski, Michael Bird, Mustafa Al-Zoughool, Nicholas Birkett, Mélissa Billard, Brittany Milton, Jerry M. Rice, Yann Grosse, Vincent J. Cogliano, Mark A. Hill, Robert. A. Baan, Julian Little, Jan M. Zielinski
The strong evidence linking genotoxicity to carcinogenesis is consistent with epidemiological data and experimental research. Genotoxic effects include the formation of DNA adducts or induction of single- and double-strand DNA breaks. Several lines of evidence from epidemiological investigations and experimental animals and model systems demonstrated that DNA adducts are strongly associated with cancer (Kriek et al. 1998; Phillips et al. 2015). Some genotoxic effects might lead to gene mutation which is an important event in the pathway towards carcinogenesis, especially if it involves oncogenes or tumor suppressor genes. Chromosomal aberrations are another type of genetic alteration that occurs frequently in many tumors, especially solid tumors. Most tumor cells display aneuploidy, and for some tumors, characteristic chromosomal abnormalities were identified including the Philadelphia chromosome in chronic myeloid leukemia.
Overview of biological mechanisms of human carcinogens
Published in Journal of Toxicology and Environmental Health, Part B, 2019
Nicholas Birkett, Mustafa Al-Zoughool, Michael Bird, Robert A. Baan, Jan Zielinski, Daniel Krewski
High doses of aristolochic acids produce severe necrosis of renal tubules, splenic and thymic atrophy and ulceration of the forestomach in animals. Aristolochic acids are consistently active in in vivo and in vitro genotoxicity tests. Metabolism of aristolochic acids leads to production of electrophilic cyclic N-acylnitrenium ions, which react with DNA to produce adducts. These adducts were identified and detected in exposed animals and in urothelial tissues from patients with nephropathy subsequent to intake of aristolochic acid. The DNA adducts may lead to mutations that activate oncogenes or inactivate tumor suppressor genes (e.g. TP53 or RAS). In rodent tumors, activation of RAS oncogenes were discovered through a specific CAA→CTA transversion mutation in codon 61. In one nephropathy patient, a similar mutation was found in codon 139, exon 5 of the RAS gene.