Acrylamide arrests mitosis and prevents chromosome migration in the absence of changes in spindle microtubules.
Cultured HT 1080 fibrosarcoma cells were exposed to acrylamide (ACR), an industrial neurotoxicant that disrupts neuronal intracellular transport, to determine if mitosis (another microtubule-based intracellular transport system) was adversely affected. The number of cells arrested in mitosis increased, in a concentration-dependent manner, from 1 to 10 mM acrylamide. A 4-h exposure to 10 mM acrylamide increased the mitotic index by 4.5-fold over control, comparable to the arrest caused by colchicine. In mitotic acrylamide-exposed cells, the chromosomes remained at the metaphase plate; no changes in spindle microtubules (MTs), as seen with tubulin immunofluorescence, were observed. The distance between spindle poles (interaster) was the same in control and experimental cells. The non-neurotoxic analogue methylene bisacrylamide had no effect in the same concentration range. The data suggest potential molecular mechanisms of action for general toxicity and neurotoxicity to be disruption in MT disassembly or MT-kinetochore interactions and/or cellular homeostasis.
Sickles
D W
DW
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912-2000.
Welter
D A
DA
Friedman
M A
MA
D020106:Acrylamide; D000178:Acrylamides / Q000633:toxicity*; D003078:Colchicine / Q000494:pharmacology; D005354:Fibrosarcoma; D005455:Fluorescent Antibody Technique; D006801:Humans; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects*; D008940:Mitotic Index; D008941:Spindle Apparatus / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000178:Acrylamides; D020106:Acrylamide; C021221:N,N'-methylenebisacrylamide; D003078:Colchicine