Ultrastructural changes in normal rat colon induced by photodynamic therapy

Despite the fact that photodynamic therapy (PDT) is a promising new technique for the treatment of gastrointestinal tumours, its effect on normal mucosa has so far received little attention. With a view to understanding the changes that occur in normal colon mucosa, we have examined the ultrastructure of normal rat colon mucosa after PDT. Female Wistar rats were treated with dihaematoporphyrin derivative (Photofrin^®) administered i.v. at a concentration of 5 mg kg^?1 body weight. Twenty-four hours after injection lesions were produced using a special device and irradiation was carried out with an argon-ion pumped-dye laser system (λ=630 nm, energy density 150 J cm^?2 and 30 J cm^?2; power density 100 mW cm^?2). At different points of time animals were sacrificed, tissues specimens were removed and a light and ultrastructural examination was carried out. At 90 min after treatment with 30 J cm^?2, superficial epithelial cells showed vacuoles in the basal part and were separating from the basement membrane. Capillaries were engored with erythrocytes and 24h after treatment there was destruction of capillaries and massive haemorrhage into the lamina propria. Immediately after treatment with 150 J cm^?2 there was sloughing of superficial epithelial cells from the basement membrane and crypt cells contained numerous vacuoles. After 24h there was complete necrosis of the mucosa. The action of PDT applied to normal rat colon mucosa is time- and energy-density-dependent and manifests as primary cytotoxic effects on superficial epithelial and crypt cells. Secondarily, there is destruction of the capillary system in the lamina propria, which leads to haemorrhagic necrosis of the mucosa.