12.3: Cancer Biology

Cancer is an uncontrolled growth of cells that can lead to death. Cancer can invade surrounding tissue and spread to vital organs. A tumor (an abnormal growth of cells that forms a lump) that spreads is called malignant (evil). The word cancer comes from the Latin word meaning crab—its threatening claws extend outwards. Benign (good) tumors don’t have this capacity to spread.

What makes a cell suddenly divide wildly and invade other tissues? From basic research into how normal cells work, genes that control cell growth have been identified. Mutations in several such genes may be needed for cancer to develop, causing a cell to grow out of control—like a car when the accelerator is stuck or the brakes are gone. Substances that cause these mutations are called carcinogens.

How cancer develops is very complex. Some examples:

• Carcinogens must reach a cell’s DNA to do damage. A cell’s sturdiness matters. Irritating or damaging a tissue can make it more vulnerable to cancer, e.g., drinking alcohol excessively raises the risk of cancer in the esophagus and liver. Also, when tissues are damaged, cells usually divide to replace the damaged cells. More cell division means more chances for mutations from DNA-copying errors (Chap. 10).

Other features of cells affect whether a cancer-causing agent can reach the DNA. Skin cancer is less common in those with naturally dark skin due to melanin, a brown/black pigment. Melanin is a natural sunblock that absorbs the ultraviolet light that can damage DNA (genetic differences in skin color vary with exposure to ultraviolet radiation in sunlight during evolution—more exposure/darker skin). Getting a tan is a protective response—skin makes more melanin to protect its DNA. Albinos can’t make melanin and are very vulnerable to skin cancer. Melanoma is a cancer of melanin- making cells.

• If a cell’s DNA has been made cancerous by a carcinogen, it won’t “become cancer” if the damage is repaired or the cell is destroyed. Cells routinely repair DNA damage, but the repair processes can be defective or overwhelmed. People with the genetic disease xeroderma pigmentosum (“no skin pigment”) lack the protective melanin in their skin, plus have defective DNA repair, making them very susceptible to skin cancer. Many get skin cancer before age 10. Defects in DNA repair have also been implicated in more common cancers (e.g., some forms of colon cancer).

Our immune system routinely destroys damaged cells. So, a deficient immune system makes us more susceptible to cancer, as happens in AIDS (Acquired Immunodeficiency Syndrome) or in taking immunosuppressive drugs to prevent rejection of an organ transplant. We probably “get cancer” often, but develop it only occasionally. As we get older, we can accumulate more mutations, and many body systems—immune system included—become less efficient.

Table 12-2: 2022 Estimated Cancer Deaths/Diagnoses

• Some viruses can cause cancer. The first one shown to cause cancer caused tumors in chickens. Peyton Rous won a Nobel Prize in 1966 for this discovery. A retrovirus (Chap. 10) could carry a cancer-causing gene and insert it into a cell’s DNA. One such retrovirus causes a rare form of leukemia, and is similar in many ways to HIV (also a retrovirus). Human papillomavirus (HPV), which isn’t a retrovirus, is sexually transmitted and can cause cervical cancer. HPV vaccine is recommended for girls and boys at age 11-12 to help prevent HPV infection that can result later in cervical cancer and other cancers (e.g., anal cancer, cancer at the back of the throat) and genital warts.
• Substances linked with cancer often can’t be neatly categorized as carcinogens. Some are not carcinogens per se, but can change into carcinogens in the body. Conversely, the body can disarm some carcinogens. Some substances are carcinogens only when paired with another substance (co-carcinogens). Some carcinogens are found in nature together with substances that protect against cancer.

Figure 12.3: Cancer Diagnosis Rates (2014-2018), Ages 35-69

Ames Test

Efforts to identify cancer-causing agents (carcinogens) often begin by screening substances to see if they are even capable of causing mutations. The Ames test does this.*

The test uses modified strains of bacteria—their cell walls have been modified to make it easier for substances to reach their DNA, and their DNA repair systems have been removed. A liver extract is also used to provide liver enzymes, so that liver-altered forms of the substance will also be tested. (Some substances aren’t carcinogens per se, but are changed into carcinogens in the body, typically by liver enzymes.)

The test includes about a billion bacteria, the test substance, products of the test substance (from the action of liver enzymes), and a nutrient broth. A key feature of the test is that the bacteria can’t make the amino acid histidine, so can’t grow because the nutrient broth has minimal histidine. If the test substance (or one of its products) causes mutations in the non-growing bacteria, mutations of all sorts occur in these billion bacteria.

In a lottery of sorts, some of these mutations will enable some bacteria to make histidine, and these bacteria will flourish. The growth of these bacteria then means that the test substance is capable of causing mutations—a potential carcinogen. The Ames test is extremely sensitive; many substances that are identified as possible carcinogens may not actually be carcinogens in “real life.”

This test has been used extensively to test chemicals already in use, as well as novel chemicals proposed for use. Besides testing to see if a chemical is capable of causing mutations, the Ames test is also used to test the chemical’s potency to do so. Highly mutagenic compounds will cause mutations at very low concentrations.

When a company requests approval for a new food additive, it must submit evidence that it’s safe and effective. Prior to the introduction of the Ames test in 1973, a proposed additive was first tested on animals to see if it caused cancer. Now, it’s first screened by the Ames test or a similar test before animal testing.

Fig 12-4: Cancer Death Rate (age-standardized): United.States vs. World Average in 2020

^{*Bruce Ames, biochemistry professor from the Univ. of Calif. at Berkeley, devised this test.}