Mucosal mitochondrial function and antioxidant defences in patients with gastric carcinoma

Abstract

Background: Cancer cells have alterations in energy metabolism due to defective mitochondrial function. This may be due to generation of excessive free radicals and/or defective antioxidant enzyme systems. The aim of the present study was to assess mitochondrial function and antioxidant defences in the gastric mucosa of patients with gastric carcinoma (CA). Methods: Gastric mucosal mitochondrial function was assessed by means of the reduction of tetrazolium dye (MTT), and levels of antioxidants such as glutathione S-transferase (GST), catalase, superoxide dismutase (SOD), and thiols were measured in biopsy specimens taken from the tumour mucosa (TM) and tumour-free (TF) mucosa, 2 cm away from the tumour, in 49 patients with gastric CA and compared with that in 54 controls. In a further 10 patients with gastric CA, these studies were done on TM and TF mucosa 2 cm and > or = 5 cm away from the tumour. In 10 patients and 5 controls, specimens were obtained for electron microscopy as well. Helicobacter pylori infection was diagnosed by means of histology. Results: MTT reduction and GST and SOD activities were significantly decreased in TM and TF mucosa in patients with CA compared with controls (P < 0.01). The levels of thiols and catalase activity were significantly increased in CA as compared with controls (P < 0.01). H. pylori positivity did not influence most of these variables but did give significant decrease in MTT reduction in CA (TF) mucosa (P=0.01) and significant increase in thiol levels in CA (TM) mucosa (P=0.04). Electron microscopy showed mitochondrial alterations in tumour cells in all patients and in adjacent mucosa of 10%-50% of the cells. Conclusions: 1) In gastric CA the cancer mucosal cells and the non-involved cells adjacent to the tumour have defective mitochondrial function, which may be due to altered antioxidant defences and possibly altered free radical formation. 2) Ultrastructural mitochondrial abnormalities are shown to parallel these biochemical abnormalities.