Repair of wounded monolayers of cultured vascular endothelial cells after simultaneous exposure to lead and zinc.

We investigated the interaction between lead and zinc on the repair of wounded monolayers of cultured bovine aortic endothelial cells. A half area of the monolayers was wounded and then incubated in the presence of lead (5.0 and 10 microM) and/or zinc (10 microM). It was morphologically observed that the appearance of the cells in the wounded area was strongly decreased by lead alone but considerably increased by zinc alone. The repair of wounded area after simultaneous exposure to lead and zinc showed that lead inhibits not only spontaneous but also zinc-promoted repair of endothelial cell layers without a change of the leakage of lactate dehydrogenase. Interaction between lead and zinc on the DNA synthesis of growing endothelial cells was similar to that on the repair, suggesting that the repair reflected the proliferation. In growing endothelial cells, the intracellular accumulation of lead was significantly increased by zinc; that of zinc was unaffected by lead; and that of metallothionein was slightly increased by zinc and lead but the effect of zinc was suppressed in the presence of lead. Although zinc significantly decreased the intracellular accumulation of radioactive calcium, lead increased it in the presence or absence of zinc. It was therefore concluded that lead inhibits not only spontaneous but also zinc-promoted repair of the damaged endothelial cell layers through an inhibition of the proliferation mediated by the calcium-mediated signalling pathways and/or a disturbance of intracellular calcium homeostasis.