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Drug resistance genes, such as MDR1, involved in drug efflux, and their regulation have been the subject of intense research efforts in the past 10 years. Many factors and cellular signalling pathways play a role in the regulation of MDR1 gene expression. Commonly used chemotherapeutic agents activate in vitro and in vivo general stress response pathways, potential targets of which include MDR1 and other drug resistance genes. The contribution of these agents to the emergence of drug-resistant tumour cells is of concern. Recent evidence points to a role for the epigenetic regulation of MDR1 gene expression. The identification of key components in the DNA methylation/chromatin system of gene regulation may in time lead to more informed and targeted approaches to treating drug-resistant tumours. Copyright 2000 Harcourt Publishers Ltd.