Industrial Chemicals and Occupational Cancers

The chemicals and industrial processes that have a known or suspected etiologic role in the development of cancer are listed in Table 3-6. As noted above, about 2 -5 of all cancer deaths are attributed to occupational hazards. Of those agents listed as carcinogenic for humans, a number were identified because of their close association between an abnormal clustering of certain cancers and exposure to an industrial chemical or process. For example, epidemiologic studies of workers occupationally...

Historical Perspectives

The development of knowledge about the biochemistry and cell biology of cancer comes from a number of disciplines. Some of this knowledge has come from research initiated a century or more ago. There has been a flow of information about genetics into a knowledge base about cancer, starting with Gregor Mendel and the discovery of the principle of inherited traits and leading through Theodor Boveri's work on the chromosomal mode of heredity and chromosomal damage in malignant cells1 to Avery's...

The Great Cancer Myths

In most polls, it is the most feared disease of all. Coupled with this are the almost daily media reports of another carcinogen or cancer risk being found in our environment that produce a setting for the sometimes hysterical fear that cancer lurks around every corner. Epidemiological pronouncements that one out of eight women will die of breast cancer or one of every four men will get prostate cancer, while perhaps having some statistical validity if everyone...

Organochlorine Compounds Polycyclic Aromatic Hydrocarbons and Breast Cancer

Environmental exposure to organochlorine compounds such as polychlorinated biphenyls (PCBs), 2,2'-bis (p-chlorophenyl)-1, 1, 1-tri-chloroethane (DDT) and its metabolite DDE, and organochloro pesticides has been suggested as a risk factor for breast cancer. The basis for this claim is that some of these are carcinogenic in animals, have estrogenic activity, and are inducers of cytochrome P-450 enzymes that metabolize drugs, hormones, and various xeno-biotics. Some epidemiological studies have...

Cervical Cancer

A large class of papillomaviruses that are pathogenic for humans (HPV) have been identified. More than 60 genotypic subtypes have been isolated.148 Only two HPV subtypes have been closely associated with cervical cancer, HPV 16 and HPV 18. The evidence for this association is the following (reviewed in Reference 149) (1) viral DNA is found in about 90 of cervical cancers (2) in most cases a specific piece of the viral DNA is integrated into the host's genome (3) the vast majority of all...

Cigarette Smoking

As noted above, epidemiologists have attributed as many as 30 of all cancer deaths to tobacco use, primarily cigarette smoking. In 2005, for example, approximately 163,000 deaths due to lung cancer were expected to occur in the United States (90,000 men and 73,000 women), making up about 31 of all deaths from cancer in men and 27 in women.3 Although the most direct correlation is between cigarette smoking and lung cancer, tobacco use has also been implicated in cancers of the mouth, pharynx,...

Angiogenesis

Development of a functional vasculature is a key event in normal embryonic development as well as in the adult for such things as wound healing, corpus luteum angiogenesis during the female reproductive cycle, and development of the placenta. The process of new blood vessel formation from mesodermal stem cells during embryonic development is called vasculogenesis (Fig. 4-32). Angiogenesis, by contrast, is the term used to describe development of new blood vessels from pre-existing ones. This is...

Air and Water Pollutants

Air, water, and soil pollution is estimated to account for only 1 -4 of all cancers. A small percentage of lung cancer (less than 5 ) may be due to chronic inhalation of outdoor air pollutants such as industrial or engine exhaust chemicals. Indoor air pollutants such as secondhand smoke and radon are thought to be contributors, but this risk is most likely exaggerated (see below). In China and some other Asian countries, chronic inhalation of cooking oil smoke may be a causative agent of lung...

Experimental Models for the Study of Carcinogenesis

A number of models for the study of carcino-genesis have been developed over the years. Historically, two of the most useful ones have been the initiation-promotion model of mouse skin carcinogenesis (the skin-painting model) and the induction of liver cancers in rats. The classic model of carcinogenesis is the single application of an initiating agent such as a polycyclic aromatic hydrocarbon followed by the continuous application of a promoting agent like TPA to the backs of shaved mice. Much...

Cancer Is a Global Problem

Cancer is clearly a worldwide problem. The incidence and mortality rates for various cancers are similar, though not identical, among developed countries. In the developing world, as countries become more westernized and their populations achieve longer life expectancy, cancer rates are increasing. Although there are differ ences among developing and developed countries in the incidence rates of certain cancers, lung cancer is the most common cancer among men in both regions of the world and...

Cell Cycle Checkpoints

The role of various CDKs, cyclins, and other gene products in regulating checkpoints at G1 to S, G2 to M, and mitotic spindle segregation have been described in detail elsewhere.156-158 Alterations of one or more of these checkpoint controls occur in most, if not all, human cancers at some stage in their progression to invasive cancer. Examples of some of these alterations are given below. A key player in the G1-S checkpoint system is the retinoblastoma gene rb. Phosphorylation of the Rb...

Oxygen Free Radicals Aging And Cancer

The diseases of aging include cardiovascular disease, decline in function of the immune system, brain dysfunction, and cancer. People living in the United States who are 65 or older have decreases with age. There is a fair amount of circumstantial evidence to support this latter hypothesis (reviewed in References 114-116). Oxidative damage to DNA, proteins, lipids, and other macromolecules accumulates with age. Oxidation products formed during normal metabolic processes in cells include...

Lymphoma

Lymphomas are generally classified as Hodg-kin's and non-Hodgkin's (NHL) lymphomas, although there are a number of subtypes of NHL that differ in their cellular morphology, response to chemotherapy, and prognosis. The new cases annually in the United States are in the range of 7300 for Hodgkin's disease and 56,000 for non-Hodgkin's.3 Deaths due to NHL are about 20,000 annually, whereas only about 1400 deaths occur from Hodgkin's disease in the United States. Globally, about 62,000 cases of...

Radon

Radon is a radioactive gas that is ubiquitous in earth's atmosphere. Itis formed from the radioactive decay of radium-236. Radium is found in substantial but varying amounts in soil and rocks and ends up in some building materials. Various parts of the country have varying amounts, as do certain localities within a small geographic area. There is extensive epidemiologic evidence that exposure to high levels of radon produces bronchogenic carcinoma (reviewed in Reference 115), most of which...

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...

Immortality of Transformed Cells in Culture

Most normal diploid mammalian cells have a limited life expectancy in culture. For example, normal human fibroblast lines may live for 50 to 60 population doublings (the ''Hayflick index''), but then viability begins to decrease rapidly unless they transform spontaneously or are transformed by oncogenic agents. However, malignant cells, once they become established in culture, will generally live for an indefinite number of population doublings, provided the right nutrients and growth factors...

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,...

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...

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...

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...

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...

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...