Pesticides and their link to Cancer

Pesticides and Cancer Introduction Pesticides are biologically active compounds used as insecticides, herbicides, and fungicides. The use of these compounds carries a significant public health concern as they pose health risks. A number of pesticides have been identified as containing substances which are thought to be carcinogenic, for example chlordane and dichlorophenyltrichloroethane (DDT).

Epidemiological studies of the population frequently exposed to high doses of these chemical substances such as farmers and manufacturers indicate elevated incidences of, “blood and lymphatic system cancers, cancers of the lip, stomach, lung, brain and prostate, as well as melanoma and other skin cancers”.

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Though pesticides are increasingly linked to carcinogenesis, there are other environmental and genetic factors that influence development of cancer. Examples of these factors are ionizing radiation and heritable disorders. These factors, however, are associated with a few percentages of childhood brain tumors. Most pesticides like organophosphates, carbamine and pyrethrin rapidly diffuse through the blood-brain barrier, hence the tendency to affect the nervous system.

Pesticides and Childhood Brain Cancer Literature Review In spite of the knowledge that chemical pesticides are involved in carcinogenesis, few studies have been carried out to assess the individual pesticides. However, in a study to investigate parental pesticides and childhood brain cancer, Shim, Mlynarek and Wijngaarden (2009) evaluated potential exposure of parents to pesticides in their occupations and reported that the risk of developing strocytoma significantly increases with the level of exposures. The researchers were informed by previous studies that show parental occupation exposures as a risk for childhood brain cancer. The previous studies, however, used a poor research design with a small study population, a heterogeneous population and poor exposure evaluation. The researchers, therefore, used population-based case-control approach whereby children identified were to have, “first primary brain cancer” (Shim, Mlynarek & van Wijngaarden 2009, p. 1002).

These were individuals diagnosed with brain cancer when they were less than 10 years old. 526 cases were enrolled with an equal number of controls bearing same characteristics as the cases, but not diagnosed as having cancer. Data was collected by interviewing the biological mothers regarding their occupations and exposure to pesticides.

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The data collected was then used to establish etiological relationship with the most common forms of brain cancer, “primitive neuroectodermal tumors (PNET) and astrocytoma” (Shim, Mlynarek & van Wijngaarden 2009, p.1003). The researchers observed that risk of having cancer, especially astrocytoma, was positively correlated with exposure to pesticides. The risk for carcinogenesis was higher for residential use of pesticides than parental exposure. The likelihood of developing astrocytoma and other forms of cancer following exposure to pesticides was higher as compared to the likelihood of developing primitive neuroectodermal tumors when considering exposure of the father. The exposure of the mother to the pesticides presented no significant risk of developing brain cancer.

Vulnerability of Children to adverse effects of Pesticides Children are the most vulnerable population to the adverse effects of pesticides. This is because they are frequently exposed to pesticides in homes, schools and the surroundings in general, and also through contaminated food and water. Children also are indirectly affected by these pesticides through parental exposure during gestation period. Exposure of children to carcinogenic pesticides predisposes them to develop malignancies such as, “leukemia, neuroblasma, Wilms’ tumor, soft-tissue sarcoma, Ewing’s sarcoma, non-Hodgikin’s lymphoma, and cancers of the brain, colorectum, and testes” (Zahm & Ward 1998, pp. 894).

The vulnerability of children to pesticides is due to their physiological characteristics such as high food consumption in relation to body weight. Pesticides may enter the body through dermal absorption, inhalation or oral absorption (Jurewicz & Wojciech, 2006). Pesticides can also enter the children’s system as a result of parental exposure, for example during breastfeeding. Exposure to pesticides before conception, during pregnancy and after birth could have an etiological relationship to carcinogenesis. Some pesticides are thought to cause mutation

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of germline cells before conception, which are then inherited by the children. During pregnancy, exposure of the mother to pesticides could increase the risk of cancer development in the child as these chemicals can cross the transplacental barrier.

The blood-brain barrier acts as an interface between the circulatory system and the central nervous system. The interface’s integrity is maintained by the endothelial cells of brain capillaries. The blood-brain barrier is characterized by, “low permeability to ions and small hydrophilic molecules, low rate of vesicular transport and highly restrictive paracellular transport” (Gupta, Agarwal & Shukla 1999, p. 174). The development of blood-brain barrier is more pronounced during late gestation and early infancy, hence exposure to pesticides impair with its normal development. Pesticides cause biochemical changes to this interface leading to pathological disorders and neurological alterations. The brain, thus, becomes predisposed to pesticide-induced damages as a result of increased uptake of xenobiotics when the blood-brain barrier is not well developed. The immature blood-brain barrier may cause accumulation of toxic substances in the central nervous system, potentially increasing the risk of brain damage.

Pesticides may cause chromosomal imbalance, hence function as carcinogenic substances during the early developmental period which is usually a period of rapid cell growth and division (Jurewicz et al., 2006).

Children are also more vulnerable to the effects of pesticides because of immature liver.

The liver, which is concerned with metabolism of pesticides, becomes fully functional after the age of five years. In the metabolism of organophosphate based pesticides, cytochrome P45 is required for activation while paraoxynase helps in inactivation. However, these enzymes become fully functional after about six months of age.

The effect of pesticides which cause cancer disease

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A number of studies have linked various pesticides to the development of cancer. It has been shown that prenatal and postnatal exposure to chlordane is related to neuroblastoma, while organophosphates are associated with carcinogenesis of aplastic anemia and acute leukemia. In the preconception period, exposure to pesticides may result into, “mutation and epigenetic modification of gene expression through DNA methylation or genomic imprinting in the sperm or egg” (Anderson et al. 2000, p. 591). Exposure during pregnancy or post partum is associated with mutation of the body cells, as well as changes in hormonal balance and the functioning of the immune system (Shim et al 2009, p. 1004), which predisposes an individual to cancer risk.

In animal studies, chemical compounds found constituting pesticides such as organophosphates, creosote and sulfallate have been shown to induce cancer while others such as organochlorines and dichlorophenyltrichloroethane have been shown to enhance tumor development. Pesticides also contain contaminants which are highly carcinogenic. Some of these contaminants are arsenic compounds and phenoxy acid. Most of the pesticides that are associated with cancer are those which interfere with the hormonal functions. Exposure to such pesticides increases the risk of developing cancer of organs such as the breast, ovary, prostate, testis, and thyroid since these organs depend on hormones to function properly. Most of the pesticides in use are lipid soluble, non-biodegradable and have the ability to interfere with the hormones. The ability to interfere with hormonal functions is mainly because they have a hormonal-like molecular structure. The mechanisms of carcinogenesis usually involve, “endocrine disruption, procarcinogen activation by detoxification enzymes and intercellular communication impairment” (Gurney et al 2001, p. 633).

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Pesticides containing diethylstilbestrol have been linked to initiation of tumorigenic growth. Diethylstilbestrol exposure is mainly by transplacental. Once the pesticides have crossed the placental barrier, they interact with developing child’s DNA, inducing carcinogenesis.

Childhood brain tumor The etiology of central nervous system cancer is still elusive, though many factors, including exposure to pesticides, are strongly associated with it. The variations in biological features, clinical characteristics and patterns of central nervous system cancers and their locality in the brain tissue indicate that carcinogenesis mechanism is distinct between children and grownups. Exposure to pesticides and genetic makeup of an individual are the major factors that determine the development of childhood brain tumor. This is because genes influence pesticide metabolism. It has been demonstrated that the risk of developing childhood brain tumor is elevated in individuals with, “a reduced ability to detoxify chlorpyrifos and diazinon” (Nielsen et al 2010, p. 144), which are constituents of most residential pesticides. This is because pesticides can affect nucleotides in the gene responsible for paraoxonase activity.

Pesticides containing N-nitroso compounds are also likely to increase the risk of childhood brain tumor. Animal studies have shown N-nitroso compounds can induce cancer development when exposed through transplacental. In acidic conditions, N-nitroso compounds get activated into nitrosamines and nitrosamides. Nitrosamides are strong alkylating agents, hence they can interact with DNA to form DNA adducts. Besides, nitrosamides do not depend on p450 to become activated. It is also thought that nitrosamide substances can cross the transplacental barrier and induce malignant changes in the developing baby (Cordier et al., 2002).

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As most pesticides possess carcinogenic and neurotoxic properties, they have the potential of inducing brain tumors in human beings. Pesticides like, “polychlorinated biphenyls, hexachlorobenzene and p, p’-dichloro-diphenyl-dichloroethylene” (Baldwin & Preston-Martin 2004, p. 121) readily diffuse through the placenta and enter the fetal system. In animal model, they have been shown to interfere with DNA and induce transformation of fetal cells to become malignant.

Organophosphates usually cause a decrease in the levels of the enzyme acetyl cholinesterase, subsequently inactivating the neurotransmitter acetylcholine. Organophosphate pesticides can also cause biochemical alteration by inhibiting the enzyme neuropathy target esterase. Additionally, organophosphate pesticides target the nervous system, and there is a potential link between exposure to these pesticides and carcinogenesis of childhood brain tumor.

The inability to breakdown organophosphates may also increase the risk of childhood brain tumor (Nielsen et al., 2005). Paraoxynase is usually found in the liver and is involved in the metabolism of acetylcholonesterase-inhibiting oxons (Cordier et al, 2002; Bunin et al, 1994; Carter et al, 2007). Paraoxynase levels are often determined by environmental exposures, especially to pesticides which may interfere with the enzyme Paraoxynase gene and subsequently affecting metabolism of organophosphates (Davis et al, 1993; Holly et al, 1998; Gupta, 2004).

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Gupta, A., Agarwal, R. & Shukla, G.S. (1999). Functional impairment of blood-brain barrier following pesticide exposure during early development in rats. Human & Experimental Toxicology, 18: 174-179.

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