Environmental chemicals may be involved in the etiology of breast
cancers. Many studies have addressed the association between
cancer in humans and agricultural
pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues.
Parathion and
malathion are organophosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many structural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the release of the
enzyme acetylcholinesterase at the synaptic junction.
Eserine,
parathion, and
malathion are
cholinesterase inhibitors responsible for the hydrolysis of body
choline esters, including
acetylcholine at
cholinergic synapses.
Atropine, a
parasympatholytic alkaloid, is used as an
antidote to
acetylcholinesterase inhibitors. The aim of this study was to examine whether pesticides were able to induce malignant transformation of the rat mammary gland and to determine whether alterations induced by these substances increase the
cholinergic activation influencing such transformation. These results showed that
eserine,
parathion, and
malathion increased cell proliferation of terminal end buds of the 44-day-old mammary gland of rats, followed by formation of 8.6, 14.3, and 24.3% of mammary
carcinomas, respectively, after about 28 months. At the same time,
acetylcholinesterase activity decreased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control animals to 3.05 +/- 0.06 U/mL; 2.57 +/- 0.15 U/mL; and 3.88 +/- 0.44 U/mL in the
eserine-,
parathion-, and
malathion-treated groups, respectively. However,
atropine alone induced a significant (p < 0.05) decrease in the
acetylcholinesterase activity from the control value of 9.78 +/- 0.78 to 4.38 +/- 0.10 for
atropine alone, to 1.32 +/- 0.06 for
atropine in combination with
eserine, and 2.39 +/- 0.29 for
atropine with
malathion, and there was no mammary
tumor formation. These results indicate that organophosphorous pesticides induce changes in the epithelium of mammary gland influencing the process of
carcinogenesis, and such alterations occur at the level of nervous system by increasing the
cholinergic stimulation.