BIOLOGY Volume 2 - A Guide to General Biology - 2004

15. HEALTH AND DISEASE

15.6. Malignant Neoplasms

In 1991, malignant diseases (cancers) accounted for 25% of all deaths in the UK, making them the second leading cause of mortality after cardiovascular pathologies. This pattern is typical of all developed countries (Section 15.2). Breast Cancer is the most common among women, whereas Lung Cancer is the most prevalent in men (Table 15.12). Overall, more than 200 Different types of malignant tumors are known to affect humans.

Class="center">Table 15.12. The ten most common types of malignant tumors in men and women in the UK. (Cancer Research Campaign, Scientific Yearbook 1995-1996.)

A malignant tumor results from uncontrolled Cell Division, or more precisely, a disruption in mitotic activity. This is triggered by Mutations or abnormal activation of genes that regulate cell division. Genes responsible for the malignant transformation of normal Cells are called oncogenes (from the Greek onkos meaning "tumor"). Around a hundred such genes have been identified. As a malignant cell divides, it gives rise to a clone of identical copies. Ultimately, these form a disorganized mass of relatively undifferentiated tissue known as a malignant tumor. Cells that break away from the primary tumor (Fig. 15.17) can be transported via the bloodstream and lymphatics to other PARTS OF THE body, where they settle and form secondary tumors, referred to as metastases. This process is called metastasis. Tumors capable of metastasizing are classified as malignant because, as they spread throughout the body, they disrupt vital Organ Systems and sooner or later lead to the patient's death. Tumors can also be benign. These are characterized by localized growth and the absence of metastasis; they are practically harmless and easily removed surgically.

Fig. 15.17. Scanning electron micrograph of cancer cells. These cells are typically large and exhibit a "fuzzy" surface, which is thought to increase their motility.

15.6.1. Causes of Tumors

Changes in genes are called mutations, and the factors that cause them are known as mutagens. A mutagen that triggers tumor development is commonly referred to as a

Retroviruses. Evidence for the genetic nature of cancer comes from studies of so-called retroviruses, whose Genetic information is encoded in RNA. Once inside host cells, retroviruses use their own enzyme, Reverse Transcriptase, to synthesize complementary DNA using their RNA as a template. This DNA integrates into the host genome and replicates alongside it from generation to generation in a form known as a provirus. While some retroviruses are harmless, the family also includes HIV and many oncogenic strains. The provirus formed by the latter contains genes that activate specific host cell genes, forcing them to divide uncontrollably and thus transforming them into malignant cells (thereby acting as oncogenes). The "advantage" for the virus is that cellular mitosis repeatedly copies its genetic material, which sooner or later leads to The production of numerous new Viral Particles.

DNA VIRUSES. Some of these viruses carry oncogenes within their DNA that induce uncontrolled division of the host cell. Examples include papillomaviruses, which encompass the causative agents of human warts and several forms of uterine cancer that can be sexually transmitted (via a shared sexual partner). The Epstein-Barr virus causes Burkitt's lymphoma, which is relatively common in Africa.

GENETIC PREDISPOSITION. Approximately 5% of human cancer cases are linked to a clear hereditary predisposition, involving over 40 types of such conditions, including breast, ovarian, and colorectal cancers. Genes associated with tumor development either directly drive the proliferation of malignant cells (i.e., oncogenes) or result in the body's inability to combat such cells. In most cases, multiple factors are required for cancer to develop; however, sometimes a single defective Gene is sufficient, as in retinoblastoma. Retinoblastoma originates in the retina of THE EYE AND spreads to the Brain, proving fatal if left untreated. The gene responsible for it is dominant.

Two genes responsible for breast cancer have been discovered: BRCA1 and BRCA2. BRCA1 was cloned in 1994 and encodes a protein involved in METABOLISM/31.html">Transcription. Approximately 80% of women carrying either of these mutated genes will develop breast cancer by the age of 70.

IONIZING RADIATION. This type of radiation includes X-rays, gamma rays, and streams of particles produced by the decay of radionuclides. As early as the beginning of the last century, it was observed that individuals working with X-rays frequently developed cancer. Increased cancer rates were also recorded among watch dial painters who used luminous paint containing radioactive radium and thorium. Ionizing radiation was found to generate highly reactive ions within cells that damage biological molecules, including DNA, thereby causing mutations. Consequently, this can lead to cancers of the skin, Bone Marrow, Lungs, and breast, among others. Diagnostic X-ray examinations (including dental X-rays) also expose patients to ionizing radiation.

ULTRAVIOLET RAYS. This is the most widespread carcinogenic radiation. UV rays cause ionization and are absorbed by DNA, giving its nitrogenous bases excess energy that allows them to engage in "unwanted" Chemical Reactions with surrounding molecules. Because ultraviolet light is a component of solar radiation, prolonged sun exposure carries a high risk of developing Various Forms of skin cancer, including melanoma. This tumor is prone to aggressive metastasis and typically causes death due to secondary growths in the brain. The depletion of the atmospheric ozone layer results in higher levels of ultraviolet radiation reaching the Earth's surface. Some protection against it is provided by the brown skin pigment melanin, which is why inhabitants of tropical regions naturally have darker skin.

RADON. Radon gas is a natural radionuclide emitted by certain rocks, such as granite. In areas with significant deposits of such rocks, it can accumulate inside buildings. Although definitive data on the carcinogenicity of radon are lacking, it is believed to contribute to The Development of leukemia (cancer of Blood-forming tissue that produces white Blood Cells), lung cancer, Kidney Cancer, and prostate cancer.

CHEMICAL CARCINOGENS. Today, a multitude of carcinogenic substances are known. The first reports concerning them—specifically soot and coal tar—appeared as far back as 1775, when it was observed that chimney sweeps had a high incidence of scrotal cancer. It was later discovered that mineral oils, particularly shale oil used as a lubricant in cotton-spinning machinery, were also carcinogenic. Workers whose skin regularly came into contact with clothing soaked in this oil frequently developed cancer. In the late 19th century, a link was established between Bladder cancer and employment in synthetic dye manufacturing plants.

The list of chemical carcinogens steadily grew throughout the 20th century and is now quite extensive. For instance, certain food additives (flavorings, colorants, stabilizers) were found to cause cancer in laboratory animals, necessitating bans on their use.

Tobacco smoke contains agents that induce lung cancer (Section 9.7), the most hazardous of which are polycyclic Hydrocarbons that are metabolized into carcinogens within the body. Carcinogens may also be present in everyday foodstuffs (Table 15.13), though their levels are typically so low as to pose no threat to health.

Table 15.13. Dietary carcinogens (Molecular and Cell Biology, Stephen L. Wolfe, Wadsworth, 1993)