Studies of the antiproliferative action of inorganic lead in relation to the phases of the rat glial cell cycle.
Inorganic lead inhibited proliferation of the C6 glial cell line with an IC(50) value of 5 x 10(-5)m-lead chloride. Cells released from a 48-hr exposure to 10(-4)m-lead chloride did not show a coherent [(3)H]thymidine incorporation on entering the S phase of the cell cycle, which suggested that they lacked synchrony. Lead did not appear to compromise DNA biosynthetic capability, since synchronous cells, obtained by mitotic selection, coherently entered S phase after a 14-hr exposure to 10(-4)m-PbCl(2). Cells maintained for 48 hr in 10(-4)m-PbCl(2) exhibited morphologies typical of an asynchronous population; however, 1 hr after release, selection of mitotic figures indicated that 35% of these cells had entered M phase. We conclude that inorganic lead has no specific antiproliferative site of action but may contribute to a lengthening of the cell cycle, the most pronounced effect being in late G2.
Cookman
G R
GR
Department of Pharmacology, University College, Belfield, Dublin 4, Ireland.
Regan
C M
CM