CHEMICAL EXPOSURES AND PARKINSONS-DISEASE IN RESIDENTS OF 3 NEGEV KIBBUTZIM

We consider whether chemical pollutants in drinking water (including a romatic hydrocarbons, alkanes, halogenated aliphatic hydrocarbons, and phthalic acid) or used occupationally in agriculture that have shown no parkinsonism-inducing effect may be responsible for excess cases of Parkinson's disease (PD) in three adjacent kibbutzim in southern Isra el (Negev). Literature data on PD pathogenesis have been compared with common pathogenetic pathways to xenobiotics effects; the following ne urotoxic mechanisms, besides individual sensitivity, have been suggest ed: (1) impairment of the protective role of the substantia nigra agai nst toxicants by binding of chemicals to melanin; (2) oxidative stress induction, including glutathione reduction, impaired calcium metaboli sm, and alteration of cytochrome P-450 activity; (3) blockade of iron chelators because of structural similarities to them or their precurso rs; (4) mediation of the production of endogenous dopaminergic neuroto xins, such as trichloroharmanes or isoquinolines; (5) blockade of dopa mine receptors because of their resemblance to chemicals with affinity to these receptors; (6) stimulation of prostaglandin-H synthase and m onooxygenase activity; and (7) stimulation of autoimmune processes and creation of autoimmunity to structures of the dopaminergic system cau sed by chemical similarity. (C) 1997 Academic Press.