Neoplasia-related changes of two copper (Cu)/zinc (Zn) proteins in the human colon

Cu/Zn-containing proteins have recently become of interest with regard to their relation with malignant disorders. Cu/Zn-superoxide dismutase (Cu/Zn-SOD) was found increased in chemically induced tumors of the large bowel whereas metallothionein (MT), containing Zn and some Cu, was shown important for the response of tumors to chemotherapy. In the present study, we evaluated the Cu/Zn-SOD and MT content of normal human colonic mucosa and colorectal carcinomas, obtained from 20 resection specimens, and of 47 adenomatous polyps. The Cu/Zn-SOD content of polyps and carcinomas was significantly (p < 0.01) elevated when compared to normal mucosa. In the adenomatous polyps the Cu/Zn-SOD content increased significantly with increasing grade of epithelial cell dysplasia, diameter, and presence of a villous component. In the carcinomas no relation was noticed between the Cu/Zn-SOD content and the Dukes' stage or the grade of differentiation.The MT content was significantly decreased in both adenomatous polyps and carcinomas when compared to that in normal mucosa. The MT content was not related to the grade of epithelial cell dysplasia of the polyps, and to the Dukes' stage or the differentiation of the carcinomas. In conclusion, neoplasia of the colorectum is accompanied by an increase in Cu/Zn-SOD and a decrease in MT. These findings support the association between changes in Cu/Zn proteins and malignancy.