Inhibition of vascular cell growth by X-ray irradiation: comparison with gamma radiation and mechanism of action.

Abstract

Catheter-based delivery of gamma and beta radiation effectively inhibits restenosis. Major disadvantages of these radioisotopes include continuous emission; excessive depth of penetration, creating safety hazards (gamma); and inadequate penetration, limiting effectiveness (beta). Low-voltage X-rays have a distinct potential advantage, because the source is active only when current is applied, and depth of penetration is voltage dependent. This study was performed to determine if low-voltage X-rays inhibit smooth muscle and adventitial cell growth in vitro and to determine the molecular mechanisms involved in this cellular response. Vascular cells in culture were exposed to low-voltage X-ray radiation and analyzed for their subsequent ability to proliferate. X-ray irradiation caused a dose-dependent inhibition in proliferation, similar to the effect seen with equivalent doses of gamma radiation. The radiation-induced inhibition of proliferation did not appear to be related to apoptosis, but rather to delayed progression through the cell cycle, because a 65% increase in the proportion of cells in S phase was seen 24-96 h after X-ray exposure compared to control. Expression of p53, a cell cycle transcriptional activator, and p21, a cell cycle inhibitor, were significantly elevated after exposure to low-voltage X-rays, providing a potential mechanism for this delay. Low-voltage X-rays can effectively inhibit proliferation of vascular smooth muscle and adventitial cells. This inhibition is apparently due to a delay in progression through the cell cycle, which is mediated by increases in the levels of cell cycle inhibitors.