Carcinogens

Methods of Testing

The first method of testing is conducted with cultured cells. In order to minimize species variation, human cells can be used. However, when an agent is evaluated in the absence of the complex nature of an entire biological system—as in the case with cultured cells—the metabolic activation of the test agent may not occur, which can result in false negatives. The main objective for using cultured cells is to test compounds by monitoring their effects on the cell functions that are involved in the process of transforming normal cells into cancer cells (i.e., DNA damage).

The second method includes testing on microorganisms. Using this method, scientists can examine the carcinogen's ability to generate mutations. The Ames test—developed by Bruce Ames in 1975—was the first method to use the bacterium Salmonella typhimurium. This bacterium was genetically altered so that it could detect chemically induced mutations. The Ames test is relatively simple to administer and can quickly examine a large number of agents. A limitation with this method is the frequent [Page 215]occurrence of false positive and false negative results. Such inaccuracies can occur because the premise behind this test is that carcinogens are also mutagens. However, this is not always the case. Therefore, the Ames test has been used by many researchers as a screening test for carcinogens prior to testing on animals.

The third and most direct method to evaluate the effect(s) of a carcinogen is through the use of animal models. These tests are conducted primarily to examine the ability of the carcinogenic agent(s) to induce cancer(s) and/or to damage the DNA of animals. However, because humans have different genetic predispositions and are not confined to various controlled environments, they often experience multiple and varied exposures to carcinogens at different doses for various durations and at different points in time throughout their lifetimes. As Curtis D. Klaassen notes, the route of exposure (ingestion, inhalation, absorption, or parenteral), as well as the carcinogen's ability to metabolize in the body, plays a role in the effect the agent has on the body. These factors make it difficult to draw parallel comparisons among humans, let alone between animals and humans.

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