The use of permanent cell lines in toxicity testing is a long established procedure Cell culture offers two major advantages over research conducted in vivo or with tissues, (1) it reduces the ethical difficulties, (2) allows environmental factors to be controlled. However, many compounds e g premutagens and precarcinogens are metabolically converted by monooxygenases and other xenobiotic-metabolizmg enzymes into their ultimate mutagemc/carcinogemc form, cultured cells rapidly lose the ability to express many of these enzymes. Therefore, a toxicological test system which intends to detect mutagens or carcinogens must be capable of producing these compounds in their ’active’ form. To overcome this lack of activation capability external activation systems have been employed (e g. hepatocytes and S9 fraction) but such systems show great variability. Some established cell lines do, however, retain a degree of their original metabolic ability making them very useful tools in toxicity testing. This project involved A) the investigation of primary culture of Non Small Cell Carcinoma of the lung. The aim of this investigation was to improve the success rate of establishing cultures, which may then be used in the determination of toxicity of chemotherapeutic agents on tumours, B) Determination of the levels of drug metabolizing activity (both phase 1 and phase 2) in a number of established cell lines under inductive pressure in order to establish the possible relevance of these lines to toxicity testing, C) To investigate the possible role of drug metabolizing enzymes in multiple drug resistance, D) To construct, by transfection, cell lines expressing the Cytochrome P4501A1 gene.