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What You Need to Know. What You Can Do.
How do scientists identify cancer-causing substances?

Learning Objective

Upon completion of this section, you will be able to

  • Explain how scientists identify cancer-causing substances.

Introduction

Over the last 30 years, scientists have worked hard to identify substances in the home, workplace, and general environment that cause cancer. This is a challenging task: in the United Sates more than 100,000 chemicals are commonly used in household cleaners, solvents, pesticides, food additives, lawn care, and other products. Every year another 1,000 or so chemicals are introduced. These are single substances that do not take into account the mixtures and various combinations of commercial and consumer products to which people in the United States are exposed every day. And many chemicals may be changed to different substances by the atmosphere, water, plants, and by incineration or combustion.

Identification of cancer-causing substances is further compounded by the fact that cancer-causing substances are sometimes created during the synthesis or combustion of other chemicals. Dioxin is an example of this kind of unwanted contaminant (see Dioxins). And besides manufactured chemicals, many natural products can also cause cancer. One example is aflatoxin (see Toxins from Fungi).

Evidence for identifying cancer-causing substances comes from three sources:

  • Human studies,
  • Animal studies, and
  • Laboratory experiments with human cells.

Evidence from each of these sources is important in helping public health officials decide whether exposure to certain substances needs to be reduced or eliminated. The more information available, the more likely it is that they will be able to identify carcinogenic substances.

Human Studies

The most certain method of identifying such substances is to observe whether they have caused cancer in people. Epidemiologists design studies that follow certain populations over time to observe whether a specific agent (e.g., arsenic or benzene) or exposure (e.g., sunlight or smoking) is likely to cause cancer. Environmental causes of cancer have frequently been first noticed in the workplace. This is because workers in certain occupations have higher exposures to particular chemicals and for longer periods of time than do the general population.

The International Agency for Research on Cancer (http://www.iarc.fr), an agency of the World Health Organization, classified certain occupations as associated with cancer-causing exposures because of the increased incidence of cancers in these settings. Some of these include

  • Painters,
  • Furniture makers,
  • Workers in the iron, steel, coal, and rubber industries, and
  • Workers involved in boot and shoe manufacture or repair.

This knowledge has helped these industries and public health specialists develop processes and safety procedures designed to minimize worker exposure to cancer-causing substances. The risk is less now than in previous years.

Yet health agencies would fail in their responsibility to prevent cancer if they merely documented workplace-related cancers. They would find out about cancer risks only after many people developed symptoms of the disease, sometimes 20 to 30 years after exposure. Other epidemiology studies compare the exposure histories of people who have developed cancer with comparison groups who have not developed cancer at a particular point in time. Such studies allow researchers to look at a wide range of past exposures that may have occurred in a variety of settings, not just at those in a particular occupational setting. But these studies may miss some important links between exposures and cancer. To determine what chemicals people were exposed to many years earlier, to what degree they were exposed, and which specific ones are harmful is often difficult. But we cannot test potential cancer-causing agents with people. Observational epidemiological studies, then, are the best source of data on real world exposures and often do provide important clues.

Other testing methods involving animals and laboratory experiments are also important. They allow scientists to anticipate potential cancer-causing exposures before those exposures result in large numbers of human cancers.

Animal Studies

Mice or rats are most commonly used to test for cancer-causing substances. Rats and mice are not only smaller, easier to handle, and more economical than larger animals; in their response to carcinogens, they are generally similar to humans. Most major forms of human cancer have been reproduced in such animals through exposure to chemical carcinogens. Because the lifetime of rodents is only 2 to 3 years, they generally provide information about the cancer-causing potential of test materials relatively quickly. Special strains of mice and rats have been developed to be particularly suitable for cancer testing. However, differences in animal and human digestive physiology complicate the relevance of diet studies in animals.

How well do animal tests predict whether a substance can cause cancer in humans?

Of the approximately 200 agents known to cause cancer in humans, nearly all have also been shown also to cause cancer in rats or mice. But how many of the several hundred other chemicals that cause cancer in animals are also human carcinogens is as yet unknown. In some instances, positive tests with mice or rats were later confirmed by the occurrence of cancer in exposed humans. In other instances, studies in human populations have failed to confirm the positive tests in mice. Most importantly, however, for many chemicals suspected of causing cancer in humans, no human studies have yet been done. Thus we do not know for sure whether these chemicals do or do not cause cancer in humans.

Yet materials that cause cancer in one type of animal have been found to cause cancer in other animals. Public health officials must therefore heed the warnings animal tests provide. Positive tests in animals are often serve as a basis for reducing or eliminating human exposure to probable cancer-causing agents., One example is when drinking water disinfectant byproducts and several solvents were shown to be carcinogenic in rats and mice. Regulatory controls to reduce human exposures were immediately established.

We often read about mice or rats being given dosages much higher than those to which humans normally would be exposed. Are such high doses really used, and if so, why?

Yes, high doses are often used to increase the ability of the tests to detect cancer-causing potential.

Large numbers of people are exposed to low doses of chemicals, but the total impact may not be small at all—a carcinogen might cause one tumor in every 10,000 people exposed to it. But exposure of 230 million Americans would result in 23,000 cancers—a public health disaster. To detect such a low cancer rate, we would need tens of thousands of mice. This would cost approximately $50 million for every chemical tested: not only expensive and time-consuming, but requiring far too many animals.

With high dosages, any potential cancerous effects are more likely detected—even in small groups of rodents. This is because the cancer rate among the test animals is increased correspondingly. If 20 or 30 of a test group of 50 mice develop cancers at much higher doses while the group not receiving the chemical has only a few cancers, the subject chemical is capable of causing cancer. When high doses do not cause cancer in animals, the greater is the assurance that the chemical will not cause cancer in people.

Experiments with Human Cells Grown in the Laboratory

As part of an ongoing effort to reduce the use of animals in cancer testing, researchers are using human cells grown in the laboratory. Cells exposed to potential carcinogens are monitored to see whether molecular changes characteristic of cancer cells develop. Besides reducing the use of animals, these kinds of studies can be done more quickly and economically and can be useful in evaluating whether to perform the studies in rats and mice. Results from laboratory experiments also provide clues to epidemiologists about which hypotheses to test in human population studies. Human observational studies evaluating the effect of exposure to formaldehyde and methylene chloride were initiated because of data from laboratory and animal studies.

In a few cases, evidence from laboratory experiments—and knowledge of the behavior of related compounds known to be carcinogenic—is strong enough to classify a chemical as a known or probable human carcinogen. Experiments using human cells helped to classify more than 200 benzidine-based dyes as human carcinogens. Benzidine had already been classified as a known human carcinogen and scientists suspected that any dye that released benzidine inside the human body would also be a human carcinogen. When human cells grown in the laboratory were exposed to a particular dye, they were able to test whether benzidine was released. Those that did were classified as human carcinogens.

In another example, one piece of data from laboratory experiments showing that it caused DNA damage in blood cells from exposed workers led to the classification of ethylene oxide (used as a starting material in the production of other chemicals and as a disinfectant and sterilant) as a known human carcinogen.

Although such studies might reduce reliance on animals in toxicology research, testing of potential carcinogens in rodents remains an important part of cancer prevention strategies. But all scientific data available for a potential carcinogen are important, and the combination of human studies, animal studies, and laboratory experiments with human cells provides scientists with the most complete understanding of chemical risks of cancer.

Key Points

  • In the United States more than 100,000 chemicals are commonly used in household cleaners, solvents, pesticides, food additives, lawn care, and other products. Every year, another 1,000 or so chemicals are introduced.
  • Besides manufactured chemicals, many natural products can also cause cancer.
  • The combination of human studies, animal studies, and laboratory experiments provides scientists with the most complete understanding of chemical risks of cancer.
  • Human studies
    • The most certain method of identifying cancer-causing substances is to observe whether those substances have caused cancer in people.
    • Environmental causes of cancer have frequently been first identified in the workplace.
    • Health agencies would fail in their responsibility to prevent cancer if they merely documented workplace-related cancers; they would find out about cancer risks only after many people developed symptoms of the disease, sometimes as long as 20 to 30 years after the exposure.
    • Other epidemiology studies compare the exposure histories at a particular point in time of people who 1) have developed cancer, with 2) comparison groups of people who have not developed cancer. Such studies allow researchers to look at a wide range of exposures that may have occurred in a variety of settings in the past—not just at those that occurred in a particular occupational setting.
    • To determine what chemicals people were exposed to many years earlier, to what degree they were exposed, and which specific chemicals were harmful is often difficult.
  • Animal studies
    • Mice or rats are most commonly used to test for cancer-causing substances because they are smaller, easier to handle, and more economical than larger animals. Also, they are generally similar to humans in their response to carcinogens.
    • Of the approximately 200 agents known to cause cancer in humans, nearly all have also been shown to cause cancer in rats or mice. But we do not know how many of the several hundred other chemicals that cause cancer in animals are also human carcinogens.
    • High doses are often used to increase the ability of tests to detect cancer-causing potential. With high dosages, any potential cancer-causing effects are more likely detected, even in small groups of rodents. This is because the cancer rate among the test animals increases correspondingly.
  • Laboratory experiments with human cells
    • Researchers use human cells grown in the laboratory as part of an ongoing effort to reduce the use of animals in cancer testing.
    • Such studies can be done more quickly and economically and can be useful in evaluating whether to perform additional or follow-up studies in rats and mice.
Progress Check

Choose the best answer.

1. Which of the following statements concerning challenges for scientists in identifying substances that cause cancer is INCORRECT?

A. Americans commonly use more than 100,000 different chemicals.
B. During the synthesis or combustion of other chemicals, cancer-causing substances are sometimes created.
C. All cancer-causing substances are manufactured as opposed to natural.
D. Every year, manufacturers introduce another 1,000 or so new chemicals.

Answer:

To review relevant content, see Introduction in this section.

2. Which of the following statements concerning sources of evidence for identifying cancer-causing substances is INCORRECT?

A. Evidence for identifying cancer-causing substances is derived IN PART from human studies.
B. Evidence for identifying cancer-causing substances is derived IN PART from animal studies.
C. Evidence for identifying cancer-causing substances is derived IN PART from laboratory experiments with human cells.
D. Evidence for identifying cancer-causing substances is derived IN PART from theoretical chemical computational calculations.

Answer:

To review relevant content, see Introduction in this section.

3. Which of the following statements concerning the role animal studies play in identifying causes of cancer in humans is INCORRECT

A. Nearly all of the approximately 200 agents known to cause cancer in humans have also been shown to cause cancer in rats or mice.
B. We do not know how many of the several hundred other chemicals that cause cancer in animals are also human carcinogens.
C. Public health officials do not have to heed the warnings provided by animal tests.
D. Positive tests in animals are often used as a basis for reducing or eliminating human exposure to probable cancer-causing agents.

Answer:

To review relevant content, see How well do animal tests predict whether a substance can cause cancer in humans? in this section.

4. Which of the following statements concerning dosage levels given to animals in testing possible cancer-causing substances is INCORRECT?

A. Mice or rats are given dosages much higher than those to which humans normally would be exposed.
B. Large numbers of people are exposed to low doses of chemicals, but the total effect may not be small at all.
C. Using high dosages, any potential cancer-causing effects are more likely to be detected—even in small groups of rodents.
D. We have greater assurance that the chemical will not cause cancer in people when LOW doses do not cause cancer in animals.

Answer:

To review relevant content, see We often read about mice or rats being given dosages much higher than those to which humans normally would be exposed. Are high doses really used and, if so, why? in this section.

5. Which of the following statements concerning use of human cells grown in the laboratory in testing for cancer is INCORRECT?

A. Experiments with human cells grown in the laboratory are not useful when evaluating whether to perform studies in rats and mice.
B. For epidemiologists, results from experiments with human cells grown in the laboratory provide clues regarding hypotheses to test in human population studies.
C. Although in toxicology research experiments with human cells grown in the laboratory might reduce reliance on animal testing, rodent testing of potential carcinogens remains an important part of cancer prevention strategies.
D. The combination of human studies, animal studies, and laboratory experiments provide scientists with the most complete understanding of the chemical risks of cancer.

Answer:

To review relevant content, see Experiments with Human Cells Grown in the Laboratory in this section.


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