Late Ultrastructural Changes in the Mouse Coronary Arteries and Aorta after Fission Neutron or 60 Co g Irradiation

Abstract

The ultrastructure of the coronary arteries and the aorta of the B6CF1 mouse from 1-24 mo. after irradiation is described. Radiation treatment, initiated at 4 mo. of age, included single total-body doses of 788 .gamma.-rad or 240 fission neutron rad and fractionated total-body doses of 823 .gamma. rad or 240 fission neutron rad (24 fractions given in 23 wk). Mice given the high .gamma. dose of 2690 rad (fractionated) and relatively low neutron doses (80 rad single and 20 or 80 rad fractionated) were studied at 18 mo after initiation of irradiation in order to increase the dose range for estimation of the relative biological effectiveness (RBE). In control mice, at 12 mo. into the experiment, there was little evidence of degeneration of the coronary arteries and aorta. At 18 mo., these vessels showed a slight amount of smooth muscle degeneration and fibrosis, while at 24 mo. lesions were more severe and there was relatively less distinction between control and treated groups (788 .gamma. rad or 240 neutron rad). Degenerative changes in the larger coronary arteries and the aorta first appeared at 3-6 mo. after irradiation and became progressively more severe at later times (12-24 mo). The major changes included smooth muscle degeneration, fibrosis and accumulations of debris and extracellular matrix. The matrix material was periodic acid Schiff (PAS) positive, indicating the presence of proteoglycans. At 12 mo., there was more focal smooth muscle degeneration in the medial layer, with some accumulation of matrix and of debris and increased amounts of collagen in the adventitial layer. At 18 mo., the medial smooth muscle showed severe damage, with accumulations of matrix material, debris and elastic and collagen fibers and there was additional fibrosis in the adventitial layer. There was little additional change at 24 mo. Coronary arterial plaques were found in several treated groups at 12-18 mo. after irradiation. The plaques appeared to involve smooth muscle proliferation and resembled lesions associated with human cardiovascular disease, except that they contained no lipid. At 18 mo. after neutron irradiation, degenerative changes in the coronary arteries and the aorta were more extensive in the groups that had received fractionated exposures than in the comparable single-dose groups. Fractionation of the .gamma. irradiation reduced the resultant damage. Comparison of fractionated fission spectrum neutron and 60Co .gamma.-ray doses indicated that the RBE for coronary artery degeneration was between 40-130. The RBE was approximately 3 for single-dose neutron and .gamma. exposures.