Cancer tissue production

In 1965 1967 a great interest has been attached to the possible role of free radicals in cancer after studies by Emanuel and his coworkers who reported the excessive production of free radicals in tumor cells (see, for example, Ref. [145]). On these grounds the authors suggested to apply antioxidant therapy for the treatment of cancer patients. Unfortunately, experimental proofs of overproduction of free radicals in cancer tissue turn out to be erroneous [146], A new interest in the role of free radicals in cancer development emerged after the discovery of superoxide and superoxide dismutases. 

The nuclei of eukaryotic cells contain multiply coiled DNA bound with proteins in bodies called chromosomes. The number of chromosomes varies with the organism. Humans have 46 chromosomes in their body cells (somatic cells) and 23 chromosomes in each germ cell, the eggs and sperm that fuse to initiate sexual reproduction. During cell division, each chromosome is duplicated and the DNA in it is said to be replicated. The production of duplicates of a molecule as complicated as DNA has the potential to go wrong and is a common mode of action of toxic substances. Uncontrolled cell duplication is another problem that can be caused by toxic substances and can result in the growth of cancerous tissue. This condition can be caused by exposure to some kinds of toxicants. 

All markers listed in Table 22.1 have been discovered by immunometric techniques by using antibodies raised against cell lines established from human cancerous tissues (i.e. CA 125) [22, 23], or against cells derived from cancer (i.e. CEA) [14], or against cells from normal tissue (PSA) [25], They in turn have generated several products which are commercially available in kits for blood determination of antigens, such as CEA and AFP that have generated more than twenty kits, or only four in the case of PSA free fraction determination. 

In Table 6-2, peak intensities of the three types of tissues are compared. It is seen that the intensities at 1,039 and 1,076 cm-1 increase in going from normal to cirrhotic to cancerous tissues. The same trend is seen in the intensity ratio of the 1,182/1,156-cm-1 bands. Since RBC contributions to these two bands are similar, this ratio can also be used for cancer diagnosis. The increased intensity of the 1,182-cm-1 band may indicate an increase in production of a-fetoprotein, which is a specific antigen for hepatoma and embryonal carcinoma. The band at 1,039 cm-1 may be due to the phenylalanine residue. Finally, the band at 1,076 cm-1 is due to the symmetric PO2 vibration of the DNA backbone (Section 4.1.2), and its increase in Raman intensity indicates an increase in the DNA concentration in cancer tissues. 

Figure 11,2. Cnilagenase activity in biopsies of nortnel humao colon, adenomas and tissue containing various Stages of cancer. Collagenase activity was expressed in terms of "specific activity," Specific activity (S.AJ Ls a standard term used by all biochemists to express enzvme activity. S.A. = milli moles of product/minute/mg protein, or some variation of this formula. The results show that normal tissue and aderromas contain little or no detectable activity, while a large fraction of the cancer tissues did contain activity, (Redrawn with permission from Liabakk ct a ., 1996 )...

One radioactive isotope of yttrium, yttrium-90, has some important practical applications. The isotope is combined with other substances to produce smart drugs. Smart drugs are drugs that detect, attack, and destroy only certain, very specific kinds of cells, such as those found in cancerous tissue. One advantage of using yttrium-90 is that it is easy to obtain. It is produced when another radioactive isotope (strontium-90) breaks down. Strontium-90 is a by-product of nuclear reactions that occur in nuclear power plants. 

In most situations, progesterone receptors are believed to be synthesized as the result of a fully functional ERP complex as an end product of estrogen-stimulated pathways in breast cancer tissue. The measurement of PRP, therefore, has also become important in predicting hormone responsiveness. Additionally, PRP is significant in predicting disease-free survival. 

Such systems are called radioisotope generators. Rn is sometimes used for the radiotherapeutic treatment of cancer. This product is isolated by separating it as a gas from the parent substance Ra which is normally in the form of solid or a solution of RaBr2. Rn grows into the radium sample with a half-life of 3.8 d. After a 2-week period, following a separation of radon from radiiun, approximately 90% of the maximum amount of radon has grown back in the radium sample. Consequently, it is useful to separate Rn each 2 weeks from the radium samples since further time provides very little additional radioactivity. The Rn is an a emitter the ther utic value comes from the irradiation of the tissue by the y-rays of the decay daughters Pb and Bi which reach radioactive uilibrium extremely rapidly with the Rn. 

Effects attributed to chlordane exposure include blood dyscrasia, hepatotoxicity, neurotoxicity, immunotoxicity and cancer. Possible mechanisms of toxicity relevant to all target organs include the ability of chlordane and its metabolites to bind irreversibly to cellular macromolecules, inducing cell death or disrupting normal cell function. In addition, chlordane may increase tissue production of superoxide, which can accelerate lipid peroxidation, disrupting the function of cellular and subcellular membranes. Chlordane induces its own metabolism to toxic intermediates, which may exacerbate its hepatotoxicity. This may involve suppression of hepatic mitochondrial energy metabolism. 

Previous reports indicating an increase of A -acetylspermidine in colorectal cancer and breast cancer tissues may be consistent with the first alternative (Takenoshita et al. 1984 Kingsnorth and Wallace 1985), although the presence of DiAcSpm in cancer tissues was only demonstrated recently. However, evidence suggesting the involvement of peritoneal macrophages in DiAcSpm production supports the second alternative (Hamaoki and Nagata 2006). 

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