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

Purpose: Catheter-based delivery of gamma and beta radiation effectively in hibits restenosis. Major disadvantages of these radioisotopes include conti nuous emission; excessive depth of penetration, creating safety hazards (ga mma); and inadequate penetration, limiting effectiveness (beta). Low-voltag e 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 smoot h muscle and adventitial cell growth in vitro and to determine the molecula r mechanisms involved in this cellular response. Methods and Results: 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, simil ar to the effect seen with equivalent doses of gamma radiation. The radiati on-induced inhibition of proliferation did not appear to be related to apop tosis, 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 transcri ptional activator, and p21, a cell cycle inhibitor, were significantly elev ated after exposure to low-voltage X-rays, providing a potential mechanism for this delay. Conclusions: Low-voltage X-rays can effectively inhibit proliferation of va scular smooth muscle and adventitial cells. This inhibition is apparently d ue to a delay in progression through the cell cycle, which is mediated by i ncreases in the levels of cell cycle inhibitors. (C) 2001 Elsevier Science Inc.