Organophosphorous and organochlorine pesticides affect human placental phosphoinositides metabolism and PI-4 kinase activity.
The objective of this work was to describe the effect of organophosphorous and organochlorine pesticides on phosphoinositides metabolism in human placenta. Pesticides concentration (10 microM) was used for in vitro incubations of cell-free homogenates labelled with (32)P orthophosphate. Heptachlor (HC) and dichloro-diphenyl-trichloroethane (o-p' DDT) increased phosphatidyl-inositol, phosphatidylinositolphosphate, and phosphatidyl-inositolbiphosphate phosphorylation while azinphosmethyl (AM) increased phosphatidylinositolbiphosphate labeling. Decreased (32)P incorporation in phosphatidylinositol was found with phosmet (PM), AM, and chlorpyriphos (CHL). The effects of these xenobiotics on PI4-kinase activity using different subcellular fractions were also examined. Both type of pesticides affected the postmembrane supernatant enzyme activity. A biphasic effect on membrane and nuclear PI4-kinase activity was seen with HC. The strongest effect found was seen with o-p' DDT in nuclear kinase activity while substantial changes were also observed in membrane. These data demonstrate the sensitivity of human placental PI4-kinase to pesticides currently found in human tissues and suggest deleterious consequences in different processes regulated by 4-phosphoinositides.
LIBIQUIMA, Universidad Nacional del Comahue, Buenos Aires 1400 (8300) Neuquén, Argentina.
María S
MS
Souza
Gladis
G
Magnarelli de Potas
Ana M
AM
Pechén de D'Angelo
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D001387:Azinphosmethyl / Q000633:toxicity; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000633:toxicity; D003634:DDT / Q000633:toxicity; D005260:Female; D006533:Heptachlor / Q000633:toxicity; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy
D007306:Insecticides; D010716:Phosphatidylinositols; D001387:Azinphosmethyl; D006533:Heptachlor; D003634:DDT; D019870:1-Phosphatidylinositol 4-Kinase; D004390:Chlorpyrifos