Sorry wordpress removed this from public viewing. Here is my act of civil disobedience and following in Sandra Steingraber’s footsteps to build awareness.
Cancer is mitosis run amuck. Instead of reproducing in careful, methodical fashion, cancer cells carry on replication and division despite a myriad of directives designed to restrain such activity. Cancer cells are dancers deaf to the choreographer. They are builders in flagrant disregard of zoning ordinances and architectural blueprints. They are defiant, disobedient, and in the view of many cancer biologists, almost purposeful in the ways they disrupt cellular biochemistry.
Besides a propensity for unrelenting growth, a cancer cell is known for two other traits: invasiveness and primitivism. The ability to invade other tissues distinguishes cancer from other freakish out-growths, such as warts. This facility operates at both a local level – cancer also ignores property lines – and a distant one, as when cancer cells are shed from the primary tumor and seeded throughout the body as metastases. Destroying healthy tissue and clogging vital passageways, both habits make cancer life-threatening.
By primitive, biologists mean that the tissues created by cancer appear to have reverted back to some earlier, cruder, unformed stage of development. They no longer bear much resemblance to the differentiated structures of which they were originally a part. Typically, the hard lump in the breast that turns out to be a malignancy is a direct descendent of one of the smooth, flat cells that wallpaper the interior surfaces of the slender mammary ducts. But, microscopically, the tumor’s mass of cells no longer looks anything like the benevolent sheets of breast epithelial tissue it came from. In general, the less a tissue resembles its previous, respectable, specialized self, the more the virulent the cancer. Along with runaway growth and the propensity to spread, this tendency to devolve into an immature, unrecognizable state is the result of a long accumulation of genetic injuries.
A cancer cell, then, is made, not born. Cancer arises through a series of incremental changes to chromosomal DNA. Some of these DNA alterations can be inherited, but the vast majority are acquired during the lifetime of an individual when genes perfectly healthy at the time of conception become damaged. This process can happen through numerous pathways. Routine errors made during DNA replication are one. Sabotage by carcinogens is another. To contribute to cancer, at least some of these encounters between carcinogens and genes must involve the handful that help govern cell division.
These growth-regulating genes come in two basic varieties. The first group are called oncogenes. In their normal state, these bits of DNA convey messages that encourage cell division. When mutated, however, oncogenes become hyperactive and ratchet up the rate of cell division. Working on exactly the opposite principle are the tumor suppressor genes. Normally, they dampen the rate of cell division. In some circumstances – as when signs of DNA damage are about – they actually halt mitosis altogether and thereby nip in the bud the possible genesis of cancerous growth. Loss or inactivation of tumor suppressor genes may contribute to the birth of a tumor. If a mutant oncogene is a stuck accelerator pedal, then damaged tumor suppressor genes are faulty brakes. Either problem can result in runaway cell growth.
Different kinds of cancers are associated with different kinds of mutations. The cells of most colon tumors, for example, turn out to contain both hyperactive oncogenes and nonfunctional tumor suppressor genes. One specific tumor suppressor gene located on chromosome 17 has been fingered in several big-ticket malignancies, including cancers of the lung, breast, colon, esophagus, bladder, brain, and bone. Indeed, alterations of this gene, named p53, may be involved in half of all human cancers. Much as a gunshot wound indicates what kind of firearm was used in the assault, the particular nature of the p53 mutation often suggests the type of carcinogen responsible for the damage. Cigarette smoke leaves one kind of lesion, ultraviolet radiation another, and exposure to vinyl chloride a third. The mutational spectrum of this gene is so broad that the lung tumors from uranium miners can sometimes be distinguished from the lung tumors of smokers simply by looking at the specific location of the mutation. Breast tumors frequently display p53 mutations in a spectrum resembling that seen in lung tumors and varying across geographic regions.
Harm can befall growth regulator genes through a whole variety of pathways. Benzo[a]pryene can adhere to a section of chromosome and, in so doing, create a DNA adduct. Like bits of chewing gum stuck to a strand of hair, adducts can cause mistakes to be made during the next cycle of DNA replication. Other carcinogens disable the spindle fiber apparatus, causing chromosomes to pull apart improperly. By these and other means, daughter cells can end up receiving mutated oncogenes and/or missing or impaired tumor suppressor genes. Alterations in other kinds of genes can abet the process. For example, DNA repair genes normally function to fix chromosomes vandalized by mutating agents or damaged accidentally during the normal course of mitosis. An injury to a repair gene is, therefore, a treacherous event, as it can lead to the accumulation of genetic lesions of all kinds. Fortunately, the carcinogenic process is lengthy and complicated, often requiring decades to unfold. It is also capable of being arrested at many points along the way.
In the language of cancer biology, the making of a cancer cell involves three overlapping stages: initiation, promotion, and progression. To become a full-blown malignancy, a cancer cell must pass through them all.
The first rite of passage, initiation, is characterized by small structural alterations to the cell’s DNA strands. Arising spontaneously or resulting from an encounter with a carcinogen, these modifications — like tiny tattoos — are swift, permanent, and subtle. A small hole here. An inconspicuous inversion there. Cells so affected remain, to the human eye, indistinguishable in shape and appearance from their undamaged counterparts. Nevertheless, many initiated cells meet an early demise through the winnowing action of apoptosis. Any agent, then, that interferes with cell death can contribute to cancer by permitting damaged cells to continue along the pathway to tumor formation.
The immune system also plays a role in the selective destruction of incipient cancer cells, which presumably reveal their hand by exhibiting biochemical traits recognizable as abnormal. At what specific stage immune cells begin to mount a reaction in not entirely clear. It is known that certain environmental contaminants, including dioxin, suppress human immunity and that immune suppression is associated with several kinds of cancers, most notably leukemias and lymphomas. Recent studies from the former Soviet Union have shown clear relationships between exposure to certain pesticides and depression of the immune system’s T cells.
Initiated cancer cells that escape detection advance to the next stage, promotion, which requires additional exposures to cancer stimulating substances. Unlike initiation, promotion unfolds over a long period and may involve no actual mutations. In general, cancer promoters encourage cells to divide not by altering the physical structure of genes but by altering the expression of their chemical messages. Genes that are normally quiescent, for example, may become activated. Estrogen, in some cases, acts as a cancer promoter. As demonstrated in lab animals, so do many organochlorine compounds. The good news is that these effects wane when such agents are removed from the body.
Quite often, cancer promoters perturb an intricate communications pathway known as signal transduction. This system consists of a team of proteins relaying messages back and forth between the perimeter of the cell and the heartwood of the nucleus. By mechanisms barely elucidated, signal transduction proteins play a key role in the timing and the coordination of cell division. Promoting agents can affect the production and behavior of these courier molecules without permanently damaging the genes that code for their manufacture. The result is an expanded cluster of abnormal cells.
Like initiation, but unlike promotion, the progression stage involves exposures that inflict physical injury to the DNA molecule. Mutations pile up. Chromosomes fall into disrepair and become increasingly unstable. Ironically, substances that act at this stage bestow on the cells they cripple some of cancer’s most fearsome abilities: the capacity to spread and invade, enhanced sensitivity to hormones, and a knack for attracting blood vessels to the growing mass of tumor cells. Some researchers believe that arsenic, asbestos, and benzene can each function as cancer progressors, under certain conditions.
Agents that contribute to cancer do not all fall neatly into the categories of initiator, promoter, and progressor. Some, like radiation, are complete carcinogens that can play all three roles by themselves. Others, such as dioxin, appear to behave as promoters at low doses and complete carcinogens at higher levels, and they may also interfere with apoptosis. Still others initiate at low doses and promote and progress when their concentration in the body rises.
These shifting biological possibilities bring with them many social implications. First, they explain why no safe dose of a carcinogen exists. They also explain why similar exposures can pose very different degrees of danger to different people. The trace presence of a cancer-promoting pesticide in drinking water, for example, may represent absolute hazard to those whose breast, prostate, colon, or bladder tissue has already been initiated by some prior event (perhaps during childhood or because of occupation) or to those rare few born with a mutated gene that predisposes them to cancer. Individuals whose genetic material has suffered less previous damage may more successfully ward off the effects of promoting agents – as would those lucky persons who happen to posses a set of metabolism genes that allows for especially efficient detoxification and excretion of promoting substances.
The implications become even broader when we consider the dozens of known and suspected carcinogens to which we are routinely exposed and which may work alone, in concert, or cumulatively anywhere along the cancer continuum. In rats, for example, DDT acts to accelerate tumors induced by an agent called 2-acetamidophenanthrene, even though neither one alone is capable of causing tumors to progress to a detectable level.
In the words of the veteran cancer biologist Ross Hume Hall, “Too often cancer research has focused on finding the last straw. It’s time we looked at all the straws.”
Living Downstream by Sandra Steingraber portions from pages 240 – 245