Pesticides

Pesticides are a group of both natural and synthetic compounds that are used to control unwanted insects, plants, fungi, and rodents. All pesticides contain biologically active compounds that are purposely designed to interfere with normal biologic processes in target organisms. The activity of these compounds may target specific plants or animals, or they may be toxic to a wide range of species. Therefore, humans exposed to certain pesticides may be at risk to the toxic effects of these compounds, including the development of certain cancers.

Aside from individuals who come into contact with pesticides through occupational exposures, the general population is exposed to pesticides through the ingestion of food and water, by absorption through the skin, or by inhalation during application. Assessing exposure through these routes is extremely difficult because many of these factors rely on lifestyle and vary tremendously on an individual basis.

The EPA's pesticide program and other national and international bodies have classified approximately 165 pesticide chemicals as known, probable, or possible human carcinogens. Currently, there is a lack of human data to support most pesticides as being definitively carcinogenic to humans (except arsenic and ethylene oxide). However, data from animal and in vitro mechanistic studies suggest many of the main components of pesticides have the potential to cause cancer in humans and are therefore classified as probable carcinogens.2

Many pesticides may cause tumors by disrupting cell proliferation, apoptosis, and cell communication and inducing oxidative stress through nongenotoxic mechanisms.12 For example, glycophosphate-based pesticides alter cell-cycle parameters in human lymphocytes.44 In another study, different chemical classes of pesticides were shown to alter cellular proliferation by activation of erbB-2/MAPK signaling pathways.45

1,1,1-Trichloro-2,2-bis(p-chlorophenyl)-ethane (DDT) is one of the most well-studied organochlorine pesticides reasonably anticipated to be a human carcinogen.2 Despite the banning of DDT in the United State in the early 1970s because of its adverse effects on wildlife, it is still produced in other countries.46 DDT is an environmentally persistent compound that has been detected at high levels in air, water, soil, plants, animals, and human tissues. A great deal of controversy surrounds the carcinogenic potential of DDT. There is an abundance of in vitro data to suggest DDT is carcinogenic; however, data from human and animal studies have been inconsistent.

DDT can interfere with normal endocrine pathways and so it is suspected to contribute to the increasing incidence of breast and prostate cancers. There is also evidence of DDT-induced tissue damage through oxidative mechanisms.47 More recently, DDT has also been shown to alter cell signaling pathways (MAPK) that regulate growth through the AP-1 transcription factor.48 DDT also activated the oncogene erb-B2 and MAPK phosphorylation in human prostate45 and breast epithelial cells,49 which correlated with cell proliferation. These results provide evidence of signaling pathways whereby environmental chemicals may alter tumorigenesis.

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