title: Toxic effects of diazinon and its photodegradation products.
abstract: The toxic effects of diazinon and its irradiated solutions were investigated using cultivated human blood cells (lymphocytes and erythrocytes) and skin fibroblasts. Ultra Performance Liquid Chromatography (UPLC)-UV/VIS system was used to monitor the disappearance of starting diazinon during 115-min photodegradation and formation of its by-products (diazoxon and 2-isopropyl-6-methyl-4-pyrimidinol (IMP)) as a function of time. Dose-dependent AChE and Na(+)/K(+)-ATPase inhibition by diazinon was obtained for all investigated cells. Calculated IC(50) (72 h) values, in M, were: 7.5x10(-6)/3.4x10(-5), 8.7x10(-5)/6.6x10(-5), and 3.0x10(-5)/4.6x10(-5) for fibroblast, erythrocyte and lymphocyte AChE/Na(+)/K(+)-ATPase, respectively. Results obtained for reference commercially purified target enzymes indicate similar sensitivity of AChE towards diazinon (IC(50) (20 min)-7.8x10(-5)M), while diazinon concentrations below 10mM did not noticeably affect Na(+)/K(+)-ATPase activity. Besides, diazinon and IMP induced increasing incidence of micronuclei (via clastogenic mode of action) in a dose-dependent manner up to 2x10(-6)M and significant inhibition of cell proliferation and increased level of malondialdehyde at all investigated concentrations. Although after 15-min diazinon irradiation formed products do not affect purified commercial enzymes activities, inhibitory effect of irradiated solutions on cell enzymes increased as a function of time exposure to UV light and resulted in significant reduction of AChE (up to 28-45%) and Na(+)/K(+)-ATPase (up to 35-40%) at the end of irradiation period. Moreover, photodegradation treatment strengthened prooxidative properties of diazinon as well as its potency to induce cytogenetic damage.
authors: Department of Physical Chemistry, Vinca Institute of Nuclear Sciences, Belgrade, Serbia.
authors: Mirjana
authors: M
authors: Colović
authors: Danijela
authors: D
authors: Krstić
authors: Sandra
authors: S
authors: Petrović
authors: Andreja
authors: A
authors: Leskovac
authors: Gordana
authors: G
authors: Joksić
authors: Jasmina
authors: J
authors: Savić
authors: Mladen
authors: M
authors: Franko
authors: Polonca
authors: P
authors: Trebse
authors: Vesna
authors: V
authors: Vasić
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000251:Adenosine Triphosphatases / Q000097:blood; D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003976:Diazinon / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D017403:In Situ Hybridization; D007306:Insecticides / Q000737:chemistry / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D010777:Photochemistry; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D007306:Insecticides; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D000110:Acetylcholinesterase; D000251:Adenosine Triphosphatases; D003976:Diazinon