Organophosphorous pesticides in breast cancer progression.
Environmental substances may be involved in the etiology of breast cancers. Many studies have found an association between cancer in humans and exposure to agricultural pesticides. Organophosphorous pesticides have been used to control mosquito plagues. Parathion and malathion, organophosphorous pesticides are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Their primary target of action in insects is the nervous system whereby they inhibit the enzyme acetylcholinesterase at synaptic junction. Atropine is a parasympatholytic alkaloid used as an antidote to acetylcholinesterase inhibitors. We have established an experimental breast cancer model, where epithelial cells in the rat mammary gland underwent a stepwise transformation into malignant cells by exposure to pesticides (Cabello et al, 2001). The aim of this work was to examine whether pesticides were able to induce progression of malignant transformation of a human breast epithelial cell line, MCF7. These results showed that parathion and malathion increased PCNA and induced mutant p53 protein expression of MCF7 cells in comparison to controls and atropine inhibited such action. These results indicated that organophosphorous pesticides can induce more changes in this malignant breast cell line, inducing another step in the progression of the transformation process and atropine on the other hand inhibited the effect of such substances.
Cabello
G
G
Research Center for the Man in the Desert, University of Tarapaca, Arica, Chile. gcabello@uta.cl
Juarranz
A
A
Botella
L M
LM
Calaf
G M
GM
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D001285:Atropine / Q000494:pharmacology; D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008294:Malathion / Q000633:toxicity; D010276:Parasympatholytics / Q000494:pharmacology; D010278:Parathion / Q000633:toxicity; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D010276:Parasympatholytics; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D010278:Parathion; D001285:Atropine; D008294:Malathion