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Gertrudis Cabello,¹ Mario Valenzuela,¹ Arnaldo Vilaxa,¹ Viviana Durán,² Isolde Rudolph,³ Nicolas Hrepic,⁴ and Gloria Calaf^1,5

¹Biology and Health Department, Faculty of Science, University of Tarapacá, Arica, Chile; ²Juan Noé Hospital, Arica, Chile; ³Pharmacology Department, University of Concepción, Concepción, Chile; ⁴Chemistry Department, Faculty of Science, University of Tarapacá, Arica, Chile; ⁵Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, New York, USA

Abstract

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. Key words: acetylcholinesterase, atropine, malathion, parathion, rat mammary cancer. Environ Health Perspect 109:471-479 (2001) . [Online 3 May 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p471-479cabello/ abstract.html

Address correspondance to G. Cabello, Departamento de Biología y Salud, Facultad de Ciencias, Universidad de Tarapacá, Velásquez 1775, Arica, Chile. Telephone: 56 58 205420. Fax: 56 58 205419. E-mail: gcabello@uta.cl

We thank S. Rauth for helpful discussions.

This work was supported by an Institutional Grant from University of Tarapacá, Arica, Chile, and Avon grant CU51470301.

Received 23 May 2000 ; accepted 14 November 2000.