Benign Neoplasms of the Colon and Rectum
Philip H. Gordon, Santhat Nivatvongs, Lee E. Smith, Scott Thorn Barrows, Carla Gunn, Gregory Blew, David Ehlert, Craig Kiefer, Kim Martens in Neoplasms of the Colon, Rectum, and Anus, 2007
One of the most difficult problems is the treatment of duodenal adenomas. Bile has been implicated in the pathogenesis of duodenal polyps in patients with FAP. FAP bile has been shown to contain an excess of carcinogens able to form DNA adducts. DNA adducts are chemical modification of DNA, formed by covalent binding of electrophilic carcinogens to DNA, which are implicated in the initiation of carcinogenesis because when they are left unrepaired they can lead to mutations. Modification of the action of these carcinogens may reduce the adduct load to the duodenum and so decrease actual duodenal polyp number. However, in the double-blind randomized placebo-controlled trial conducted by Wallace et al. (170), 26 patients with FAP were randomly assigned to ranitidine, 300 mg daily, or placebo for six months after baseline endoscopy. The result showed that acid suppression therapy does not seem to improve duodenal polyposis.
Methods for Genetic Testing I
Peter G. Shields in Cancer Risk Assessment, 2005
There are many types of DNA damage that can be detected using molecular genetical methods, such as carcinogen–DNA adduct detection. Chemicals or their reactive metabolites can bind to DNA, resulting in promutagenic lesions. The combination of the chemical and the nucleotide is an adduct. The measurement of DNA adducts allows for the distinction between the measurement of chemicals in the environment and exposures inside the body and in target organs, because the former is not always indicative of the latter. DNA adducts reflect the biologically effective dose of an exposure, resulting from the competition of exposure, absorption, activation, detoxification, and DNA repair. Thus, the measurement of DNA adducts reflects both exposure and inherited susceptibilities. Elevated levels of DNA adducts have been correlated with cigarette use (58), occupational exposures to poly-cyclic aromatic hydrocarbons (59), and air pollution (60).
Which women develop vulvar cancer?
Miranda A. Farage, Howard I. Maibach in The Vulva, 2017
Berenblum (67) reviewed a lifetime spent studying carcinogenesis and recalled that the earliest scientific work concentrated on induction/promotion stages with viral oncogenesis, the consequences of hormonal compounds on breast tissue, and the carcinogenic properties of polycyclic aromatic hydrocarbons and aminoazo compounds; Yamagiwa of Japan produced cancers with coal tar. We now recognize that cigarette smoke causes damage via polycyclic aromatic hydrocarbons that react with DNA to form characteristic “adducts.” Levels of DNA adducts can be measured using a 32P post-labeling method (68–70) or by an immunohistochemical method (71). Differences in DNA adduct levels between smokers and nonsmokers have been reported for the cervix (72–74), anus (75), and vulva (76–78). Although the majority of my VIN patients were smokers, there were some who were not and had never smoked. My colleagues and I postulated that some who had raised levels of DNA adducts in vulvar biopsies may have been passively exposed via seminal fluid, environmental exposure, or diet. Pott was aware that many chimney sweeps were exposed to soot at a young age and did not develop cancer. Similarly, exposure to seminal fluid containing possible carcinogens may require cofactors such as HPV and critical polymorphisms or genotypes of cytochrome P450 or glutathione-S-transferase (79–81) before the carcinogenic process could be induced or promoted.
Augmentation of diethylnitrosamine–induced early stages of rat hepatocarcinogenesis by 1,2-dimethylhydrazine
Published in Drug and Chemical Toxicology, 2019
Charatda Punvittayagul, Arpamas Chariyakornkul, Teera Chewonarin, Kanokwan Jarukamjorn, Rawiwan Wongpoomchai
It is well established that DNA adducts can lead to gene mutation and subsequently induce carcinogenesis (Rundle 2006, Swenberg et al. 2011). O6-methylguanine is one of the major types of DNA adducts induced by alkylating carcinogens (Kondo et al. 2010). In the present study, the levels of colonic DNA adducts were increased in all carcinogen treated groups. Although DEN induced colonic DNA adducts formation, it did not induce ACF formation, suggesting that these adducts might be involved in neither oncogenes nor tumor suppressor genes. The combined treatment with DEN and DMH significantly increased hepatic DNA adduct formation, whereas colonic DNA adducts did not differ from DEN or DMH alone groups. This may be one reason why DMH promoted DEN-induced hepatic GST-P positive foci formation.
Toxicological profile of lipid-based nanostructures: are they considered as completely safe nanocarriers?
Published in Critical Reviews in Toxicology, 2020
Asaad Azarnezhad, Hadi Samadian, Mehdi Jaymand, Mahsa Sobhani, Amirhossein Ahmadi
Free radicals can react with DNA and cause cross-links that lead to the formation of 8-hydroxydeoxyguanosine DNA adducts (8-OHdG). This metabolite resulting from oxidative stress damage has a mutagenic potential and has been observed to be accumulated in breast tumor cells. Therefore, its measurement can be used as a marker to evaluate the genetic toxicity of different materials (Gharagozloo et al. 2016). Detection of the 8-OHdG DNA adduct can be performed by various methods; however, the most sensitive methods are HPLC and gas chromatography coupled with mass spectrometry (GC-MS) based techniques. Antibody-based techniques such as immunofluorescence, immunohistochemistry or DNA dot blots which involve the detection of an antibody attached to the 8-OHdG adduct might also be used as the alternative approached of 8-OHdG adduct detection (Ng et al. 2010).
Similarities in mRNA expression of peripheral blood drug metabolizing enzymes and cancer marker genes with biopsy samples of head and neck cancer patients
Published in Biomarkers, 2019
Feza Hasan, Tridiv Katiyar, Shailendra S. Maurya, Vinay Yadav, Sanjay Yadav, Rahul Pandey, Divya Mehrotra, Rahat Hadi, Sudhir Singh, Madan L. Bhatt, Devendra Parmar
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer, representing about 6% of all cases worldwide (Argiris et al.2008). It is well established that tobacco and alcohol are involved in the etiology of HNSCC, though not all tobacco or alcohol users develop HNSCC (Hashibe et al.2009). Majority of the chemical ingredients present in tobacco undergo metabolic activation by cytochrome P450s (CYPs), the major phase I drug metabolizing enzymes (DMEs) to reactive intermediates to exert carcinogenicity. These intermediates if not detoxified by glutathione-S-transferases (GSTs) and other phase II DMEs, bind to tissue macromolecules to produce carcinogenicity (Enoch and Cronin 2010). Formation of DNA adducts, in particular, leads to mutations in oncogenes and represent initiating event of carcinogenesis (Wiencke 2002). In addition to genotoxic effects, non-genotoxic effects also act synergistically in increasing risk to cancer in tobacco induced malignancies by modulating cellular processes through receptor activation and signalling pathways (Chen et al.2011). Genetic polymorphism in CYPs and GSTs has also been reported to increase the risk to tobacco-induced HNSCC and lung cancer (Sato et al.2000, Ruwali et al.2009, Singh et al.2009). Studies from our laboratory have suggested that gene–environment interactions play a significant role in modifying the susceptibility to HNSCC (Maurya et al.2014).
Related Knowledge Centers
- DNA
- DNA Repair
- DNA Replication
- Molecular Genetics
- Oxidative Stress
- Carcinogen
- Carcinogenesis
- Biomarker
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- Steric Factor