A rat mammary tumor model induced by the organophosphorous pesticides parathion and malathion, possibly through acetylcholinesterase inhibition

Environmental chemicals may be involved in the etiology of breast cancers. Many studies have addressed the association between cancer in humans and ag ricultural pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues. Parathion and malathion are organo phosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many st ructural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the releas e of the enzyme acetylcholinesterase at the synaptic junction. Eserine, par athion, and malathion are cholinesterase inhibitors responsible for the hyd rolysis of body choline esters, including acetylcholine at cholinergic syna pses. Atropine, a parasympatholytic alkaloid, is used as an antidote to ace tylcholinesterase 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 incr ease the cholinergic activation influencing such transformation. These resu lts showed that eserine, parathion, and malathion increased cell proliferat ion 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, a fter about 28 months. At the same time, acetylcholinesterase activity decre ased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control a nimals 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. Howe ver, atropine alone induced a significant (p < 0.05) decrease in the acetyl cholinesterase 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 +/- 0.23 for atropine with malathion, and there was no m ammary tumor formation. These results indicate that organophosphorous pesti cides induce changes in the epithelium of mammary gland influencing the pro cess of carcinogenesis, and such alterations occur at the level of nervous system by increasing the cholinergic stimulation.