In a study of 14 cancer cell lines from diverse tissues treated with a panel of 19 chemotherapeutic agents, MTX resistance was directly related to the enzymatic activity of glutathione reductase and thioredoxin reductase but not to the intracellular concentration of GSH, which, in turn, was associated with ThioTEPA (an alkylating agent) and doxorubicin resistance (87). The gene discussed is GSR; the disease is cancer.