Effects of acrylamide on primary neonatal rat astrocyte functions.
The present study assessed biochemical endpoints indicative of acrylamide toxicity in astrocyte cultures derived from neonatal rat pups. Given earlier reports on the possible ability of acrylamide to induce astrocytomas in the Fischer 344 rat, we performed studies in neonatal rat astrocyte cultures from the Fischer 344 to assess the ability of acrylamide to induce astrocytic proliferation. Measurements on astrocytic proliferation included [3H]-leucine incorporation, [3H]-thymidine incorporation, and changes in proliferating cell nuclear antigen (PCNA). Although acrylamide (0.1 and 1 mM for 7, 11, 15, or 20 days) did not significantly (P > 0.05) affect [3H]-leucine or [3H]-thymidine incorporation, it significantly (P < 0.05) increased PCNA protein expression in astrocytes exposed to acrylamide for 15 and 20 days. Additional studies revealed that this effect on PCNA protein expression was not associated with activation of dopamine-2 (D2) receptors, given that quinpirole (10 microM added to cultures for the last hour of 7, 11, 15, or 20 days in culture), a selective D2 receptor agonist, did not produce results analogous to those seen with acrylamide treatment. Cotreatment of astrocytes with acrylamide (7, 11, 15, or 20 days) and the D2 receptor antagonist, sulpiride (1 microM for the last 6 h of exposure), also failed to reverse acrylamide's effect on PCNA protein induction. Taken together, these studies suggest that acrylamide promotes astrocytic cell proliferation in the CNS even though DNA synthesis did not appear stimulated.
Aschner
Michael
M
Department of Pediatrics and Pharmacology, B-3307 Medical Center North, Vanderbilt University Medical Center, 1162 21st Avenue South, Nashville, Tennessee 37232-2495, USA. michael.aschner@vanderbilt.edu
Wu
Qi
Q
Friedman
Marvin A
MA
D020106:Acrylamide / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001253:Astrocytes / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D018492:Dopamine Antagonists / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D018492:Dopamine Antagonists; D004852:Epoxy Compounds; D009419:Nerve Tissue Proteins; D018809:Proliferating Cell Nuclear Antigen; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D020106:Acrylamide; C071834:glycidamide; D013469:Sulpiride; D004247:DNA; D007930:Leucine; D013936:Thymidine