Organophosphates and Mammary Tumors

A Review of: Cabello G, Valenzuela M, Vilaxa A, Duran V, Rudolph I, Hrepic N, Calaf G. A rat mammary tumor model induced by the organophosphorous pesticides parathion and malathion, possibly through acetylcholinesterase inhibition. Environmental Health Perspectives: 2001, 109(5), 471-479.

The environmental links to breast cancer has been a subject of great controversy. The increasing incidence of breast cancer, the fact that estrogens are known to cause breast cancer, and some research linking certain pesticides and other chemicals with breast cancer has formed the foundation for concern. Rodents are a common model for mammary cancers, in part because the differentiation of the milk ducts in rats has some similarities with human breast development. The organophosphate pesticides are not considered estrogenic. These common insecticides interfere with the enzyme acetylcholinesterase, resulting in prolonged cholinergic stimulation in the nervous system. There is some evidence that cholinergic stimulation promotes cell proliferation, thereby representing possible tumor promotion.

In this study, the insecticides parathion and malathion were given to rats by injection. The doses were far higher than environmental levels, but were not high enough to cause life-threatening toxicity in the animals. In two short-term studies, the proliferation of the milk duct structures was examined in animals dosed for only five days starting at age 16 days and at age 39 days). At the younger age, there were no significant effects on the milk ducts. However, at the older age, there was a far greater concentration of immature milk duct components, and far fewer mature mammary gland structures in parathion and malathion-treated animals compared to controls. This experiment showed a period of vulnerability in the rat during which these pesticides inhibit the normal development of the mammary glands. A third experiment dosed rats for five days starting during the period of vulnerability (age 39 days). The animals were then checked regularly for 28 months.

None of the unexposed control animals developed mammary tumors. Mammary tumor incidence in the parathion-treated rats was 14.3% and in malathion-treated animals was 24.3%. The study confirmed that the tumors were related to cholinesterase because treating the animals with atropine (which acts to oppose the cholinergic effects of the organophosphates) allowed the milk ducts to develop more normally and prevented the mammary cancers. This well-designed study indicates that the cholinergic effects of organophosphate pesticides may, at sufficiently high exposure levels, promote the development of mammary tumors. The relevance of this finding to humans, and the exact mechanism of action, must await additional research.

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