ENHANCED EXPRESSION OF CYTOCHROME-P450 IN STOMACH-CANCER

The cytochromes P450 have a central role in the oxidative activation a nd detoxification of a wide range of xenobiotics, including many carci nogens and several anti-cancer drugs. Thus the cytochrome P450 enzyme system has important roles in both tumour development and influencing the response of tumours to chemotherapy. Stomach cancer is one of the commonest tumours of the alimentary tract and environmental factors, i ncluding dietary factors, have been implicated in the development of t his tumour, This type of tumour has a poor prognosis and responds poor ly to current therapies. In this study, the presence and cellular loca lization of several major forms of P450, CYP1A, CYP2E1 and CYP3A have been investigated in stomach cancer and compared with their expression in normal stomach. There was enhanced expression of CYP1A and CYP3A i n stomach cancer with CYP1A present in 51% and CYP3A present in 28% of cases. In contrast, no P450 was identified in normal stomach. The pre sence of CYP1A and CYP3A in stomach cancer provides further evidence f or the enhanced expression of specific forms of cytochrome P450 in tum ours and may be important therapeutically for the development of antic ancer drugs that are activated by these forms of P450.