Irradiation Carcinogenesis

A number of the points made about chemical carcinogenesis are also true for radiation-induced carcinogenesis. Both X-rays and ultraviolet (UV) radiation, for example, produce damage to DNA. As with chemical carcinogens, this damage induces DNA repair processes, some of which are error prone and may lead to mutations. The development of malignant transformation in cultured cells after irradiation requires cell proliferation to ''fix'' the initial damage into a heritable change and then to allow...

Info

Ten leading cancer types for estimated new cancer cases and deaths, by sex, United States, 2005. *ExcIudes basal and squamous cell skin cancers and in situ carcinoma except urinary bladder. Estimates are rounded to the nearest 10. Percentage may not total 100 due to rounding. (From American Cancer Society, Surveillance Research, 2005. CA Cancer J Clin 2005 55 10-30, with permission.) the age-adjusted cancer death rates in men have only increased 54 in men and not at all for women.2...

Cell Extracellular Matrix and Cell Cell Adhesion

Cells in tissues are attached to one another and to the ECM. Disruption of these adhesion events leads to increased cell motility and potential invasiveness of cells through the ECM. In addition, most cell types require attachment to the ECM for normal growth, differentiation, and function. This attachment is responsible for what is termed anchorage dependence. Normal cells that are detached from their binding to the ECM undergo apoptosis, whereas tumor cells that are less dependent on this...

Molecular Genetics

Chromatin Structure and Function 258 Components of Chromatin 258 Chemical Modifications of Chromatin-Associated Proteins 259 Packaging of Chromatin 262 Structure and Function of Interphase Nuclease Sensitivity 267 Transcriptional Activation and the Cancer Connection 268 Control of Gene Expression during Embryonic Stem Cell Differentiation 269 Split Genes and RNA Processing 270 Gene Amplification 277 Cis-Acting Regulatory Elements Transcription Factors 282 Structural Motifs of Regulatory General...

Cancers Cell Phones

The use of cell phones has increased rapidly in the past few years. They are found in most parts of the world, even in remote areas of developing countries. Cell phones emit radiofrequency (RF) signals in a range between 800 and 2000 MHz, which puts it in the microwave range of the electromagnetic spectrum. RF radiation at sufficiently high levels can produce heat by inducing small electric currents. A typical cell phone operates with a power output that could only cause, at a maximum, a rise...

Validity of Tests for Carcinogenicity

There is quite a bit of debate among scientists and regulatory agencies about how to assess the carcinogenic hazards of chemicals, both man-made and natural, in our environment. Much of this debate has spilled over into the media, generating a sort of carcinogen-of-the-month club'' and much confusion among the public. Indeed, as one observer put it, ''Cancer news is a health hazard.''93 For many years, the prevailing view among cancer epidemiologists has been that 60 to 90 of human cancers are...

SV40 Virus in Early Polio Vaccines

Polio vaccines have been blamed for everything from initiating the AIDS epidemic to being a Western plot to subvert the developing world. Poliovirus vaccines that were used during the late 1950s and early 1960s were contaminated with simian virus 40 (SV40), a monkey virus that came from the monkey cells in which early batches of the vaccine were grown. A survey done in 1961 indicated that about 90 of U.S. citizens younger than 20 years of age (those born between 1941 and 1961) had received at...

Endogenous Carcinogenesis

An important question that arises is, what is the source of mutations in the human genome that leads to cancer One might argue that the answer is obvious. We live in a sea of carcinogens PAHs from automobile exhaust, industrial pollution, pesticide residues in foods, chlorinated organic compounds in drinking water, etc. Furthermore, epidemiologists argue that almost 30 of human cancers are related to cigarette smoking. Yet, a significant amount of cancers occur in people with no clear evidence...

Basic Facts About Cancer

Cancer is a complex family of diseases, and carcinogenesis, the events that turn a normal cell in the body into a cancer cell, is a complex multistep process. From a clinical point of view, cancer is a large group of diseases, perhaps up to a hundred or more, that vary in their age of onset, rate of growth, state of cellular differentiation, diagnostic detectability, invasiveness, metastatic potential, response to treatment, and prognosis. From a molecular and cell biological point of view,...

Fibroblast Growth Factor

Using initiation of DNA synthesis in mouse 3T3 fibroblasts to monitor purification, Gospodar-owicz246 isolated from bovine pituitary a mito-genic polypeptide, which he called fibroblast growth factor (FGF). Distinct from the IGFs, FGF is a potent mitogen for 3T3 cells and other cultured fibroblasts however, by itself it is only about 30 as potent as whole serum. A combination of FGF and glucocorticoids will replace whole serum as a growth promoter for some cell lines (e.g., 3T3) but not for...

Megmegakaryocytes Function

Abbreviations B, B lymphocytes G, granulocytes E, erythroid cells Eo, eosinophils M, macrophages Mast, mast cells Meg megakaryocytes NK, natural killer cells Stem, stem cells T, T lymphocytes. Abbreviations B, B lymphocytes G, granulocytes E, erythroid cells Eo, eosinophils M, macrophages Mast, mast cells Meg megakaryocytes NK, natural killer cells Stem, stem cells T, T lymphocytes. and M-CSF fosters macrophage colony growth. In addition to stimulating progenitor cell proliferation and cellular...

Biology Of Tumor Metastasis

The ''Classic'' Theory of Tumor Metastasis In humans, the earliest detectable malignant lesions are often referred to as in situ cancers (Fig. 4-33). These are small tumors (usually only a few millimeters in diameter) that are localized in tissues. They are usually detected only if they can be endoscopically or directly visualized, for instance, as in the case of carcinoma in situ of the uterine cervix, urinary bladder, or skin, or by examination of biopsy material, as for ductal carcinoma in...

Cervical Cancer

This is almost two different diseases one in the developing world and a different one in the developed world, although the etiology is similar. For example, in the United States and other developed nations, routine PAP smears and gynecologic examinations detect the majority of cases early and the cure rate is close to 100 for patients with pre-invasive lesions (cervical intraepithelial neoplasia, CIN). The cure rate is 92 for localized carcinomas that are minimally invasive.4 However, it is a...

Avoidability Of Cancer

If, as a number of cancer epidemiologists contend, lifestyle accounts for about 80 of all malignant cancers, then presumably the same proportion of cancers should be avoidable. To be more specific, about 30 of all cancers are thought to be related to smoking, 3 to alcohol consumption, 30 to diet, 7 to sexual and reproductive patterns, and another 5 to occupational hazards and industrial products.50,51 Moreover, about1 are estimated to be related to drugs and medical procedures (primarily...

Description of Cancer

Cancer is a group of diseases of higher multicellular organisms. It is characterized by alterations in the expression of multiple genes, leading to dysregulation of the normal cellular program for cell division and cell differentiation. This results in an imbalance of cell replication and cell death that favors growth of a tumor cell population. The characteristics that delineate a malignant cancer from a benign tumor are the abilities to invade locally, to spread to regional lymph nodes, and...

References

Moolgavkar Multistage carcinogenesis and the incidence of colorectal cancer. Proc Natl Acad Sci USA 99 15095, 2002. 2. P. C. Nowell and D. A. Hungerford A minute chromosome in human chronic granulocytic leukemia. Science 132 1497, 1960. 3. J. D. Rowley A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 243 290, 1973. 4. A. G. Knudson Two genetic hits (more or less) to cancer. Nat Rev...

Mucins

Mucins are a type of highly glycosylated glycoproteins that a variety of secretory epithelial cells produce. They are 50 to 80 carbohydrate by weight and function to lubricate and protect duc-tal epithelial cells. They contain O-linked glycans serine- and threonine-linked of various lengths and structures, depending on the tissue type in which they are produced. They are made in a wide variety of tissues, including the gastrointestinal tract, lung, breast, pancreas, and ovary. Tumors arising in...

Aromatic Amines And Amides

2-Acetylaminofluorene AROMATIC HYDROCARBONS Benzo a pyrene 2,3,7,8-Tetrachlorodibenzo-p -dioxin Polychlorinated biphenyls Asbestos fibrous silicates N-NITROSO COMPOUNDS N-Nitrosodimethylamine OLEFINS Ethylene oxide Vinyl chloride VC Trichloroethylene PARAFINS AND ETHERS 1,2-Dichloroethane Bis chloromethyl ether Mustard gas sulphur mustard Nitrogen mustard these CYPs Fig. 2-7 . Some of these compounds are further activated by subsequent steps for example, 2-acetylaminofluorene AAF is further...

Macroscopic And Microscopic Features Of Neoplasms

The pathologist can gain valuable insights about the nature of a neoplasm by careful examination of the overall appearance of a surgical specimen. Often, by integrating the clinical findings with macroscopic characteristics of a tumor, a tentative differential diagnosis can be reached. Also, notation of whether the tumor is encapsulated, has extended through tissue borders, or reached to the margins of the excision provides important diagnostic information. The location of the anatomic site of...

Oligosaccharide Processing Enzymes

The substitution of additional carbohydrate moieties on blood group-related structures is not the only aberrant modification of glycoproteins or glycolipids observed in cancer cells. Increased branching of asparagine-linked oligosaccharides and incomplete processing of these oligosaccha-rides have also been noted in certain cell-surface as well as secretory glycoproteins.44,45 The increased activity of specific N-acetylglucosaminyl transferases in tumor cells appears to be responsible for the...

Loss of Anchorage Dependence

Most freshly isolated normal animal cells and cells from cultures of normal diploid cells do not grow well when they are suspended in fluid or a semisolid agar gel. If these cells make contact with a suitable surface, however, they attach, spread, and proliferate. This type of growth is called anchorage-dependent growth. Many cell lines derived from tumors and cells transformed by oncogenic agents are able to proliferate in suspension cultures or in a semisolid medium meth-ylcellulose or...

Acetylaminofluorene

Hydroxy Aaf

The metabolic interconversions of this compound were studied in detail by the Millers and colleagues.9,10 In 1960, it was shown that AAF is converted to a more potent carcinogen, N-hydroxy-AAF, after the parent compound was fed to rats. Although both AAF and N-hydroxyl-AAF are carcinogenic in vivo, neither compound reacted in vitro with nucleic acids or proteins, suggesting that the ultimate carcinogen was another, as-yet Figure 2-5. Structures of some known carcinogens. Used with permission....

Characteristics Of

Patients 3 Physicians and Health Care Description of Cancer 4 What Significant Events Have Happened in Cancer Research in Hallmarks of Malignant Diseases 9 Classification of Human Cancers 12 Macroscopic and Microscopic Grade and Stage of Neoplasms 14 Histologic Grade of Malignancy 14 The Theory of Hits 17 Historical Perspectives 19 Metabolic Activation of Chemical Donors of simple alkyl groups 21 Cytochrome P-450-mediated activation 21 Polycyclic aromatic hydrocarbons 24 Interaction of Chemical...

Alcohol

Alcohol is thought to interact with smoking in the causation of certain cancers, particularly oral and esophageal cancers. Alcohol appears to be synergistic with tobacco in causing cancers of the mouth, pharynx, larynx, and esophagus, but not that of the lung.64,65 In liver cancer, there is good evidence that alcohol consumption sufficient to cause cirrhosis of the liver increases the incidence of liver cancers, perhaps secondary to the chronic damage to the liver caused by alcohol abuse. Pure...

Tgfbr2

Putative genetic pathways in colorectal cancer. It is thought that most tumors develop according to the original Vogelstein model bold arrows . MHAP, mixed hyperplastic adenomatous polyps. From World Cancer Report,1 with permission. Figure 3-6. Putative genetic pathways in colorectal cancer. It is thought that most tumors develop according to the original Vogelstein model bold arrows . MHAP, mixed hyperplastic adenomatous polyps. From World Cancer Report,1 with permission. that in...

Hallmarks Of Malignant Diseases

Cancer Rate Death Rate Male

Malignant neoplasms or cancers have several distinguishing features that enable the pathologist or experimental cancer biologist to characterize them as abnormal. The most common Figure 1-3. Annual age-adjusted cancer death rates among males for selected cancer types, United States, 1930 to 2001. Rates are age adjusted to the 2000 U.S. standard population. Because of changes in ICD coding, numerator information has changed over time rates for cancers of the lung and bronchus, colon and rectum,...

Central Dogma Of Tumor Progression

The standard concept of how cancer starts is that malignant tumors arise from a single cell transformed by a chemical carcinogen, onco-genic virus, radiation damage, endogenous genetic damage caused by oxidative insult to DNA, or any of a host of other potential ways e.g., chronic infections with a bacteria such as H. pylori or with a parasite such as schistosomiasis, or hormonal imbalance . Once the initiated cell starts to undergo clonal expansion, it undergoes multiple genetic changes, due...

Tumor Initiation Promotion and Progression

The idea that development of cancer is a multistage process arose from early studies of virus-induced tumors and from the discovery of the cocarcinogenic effects of croton oil. Rous and colleagues found that certain virus-induced skin papillomas in rabbits regressed after a period of time and that papillomas could be made to reappear if the skin was stressed by punching holes in it or by applying such irritant substances as turpentine or chloroform. These findings led Rous and his associates to...

Historical Perspectives

Image Stop Smoking

Carcinogenic chemicals and irradiation ionizing and ultraviolet are known to affect DNA and to be mutagenic under certain conditions. Thus, one of the long-standing theories of car-cinogenesis is that cancer is caused by a genetic mutation however, it is now known that epige-netic mechanisms are also involved. Evidence that chemicals can induce cancer in humans has been accumulating since the sixteenth century reviewed in Reference 7 . In 1567, Paracelsus described a ''wasting disease of...

A A

Adenoma Carcinoma Sequence

Two-hit tumor formation in both hereditary and nonhereditary retinoblastoma. A one-hit clone is a precursor to the tumor in nonhereditary retinoblastomas, whereas all retinoblasts indeed, all cells are one-hit clones in hereditary retinoblastoma. From Knudson,4 reprinted by permission from Macmillan Publishers Ltd. reported the development of urinary bladder cancer in aniline dye workers in Germany. Similar observations were later made in a number of countries and established a...