Flavonoids are phenolic compounds that are widely distributed in higher plants and form part of the human diet. These beneficial chemicals have potential applications as antiinfective and anti-inflammatory agents, as well as in the treatment of conditions such as cancer, hypertension, hypercholesterolaemia, and others. Studies on closely related flavonoids (e.g., quercetin, naringenin, apignein, myricetin, luteolin, and hesperetin), have demonstrated that minor structural differences influence the range of biological activities of these polyphenols. However, details on the molecular targets and the mechanism of action of these compounds have not been elucidated. The general goal of this grant proposal is to identify genes that are uniquely expressed in response to treatment of cells with closely related flavonoids. Standard techniques for concurrently isolating multiple differentially expressed genes, such as subtraction, and differential hybridization require large quantities of messenger RNA (mRNA) and are both time consuming and labor intensive. A relatively new method, differential mRNA display, greatly reduces the time and materials needed for such procedures. Additionally, by comparing the patterns of expressed mRNAs, both qualitative and quantitative changes can be detected. The specific aims of this grant proposal are to: (I) Use the differential display reverse transcription polymerase chain reaction (DDRT-PCR) to isolate specific genes that are induced, inhibited or quantitatively modulated in response to treatment of cells with quercetin. (2) Use the differential display to begin the identification of genes that are induced, inhibited or quantitatively modulated in response to treatment of cells with closely related flavonoids, myricetin, apignein, luteolin, naringenin, and hesperetin. The identification of genes that are modulated in response to flavonoids will provide a direct comparison of the effect of structural differences on gene expression among these agents, and identify novel therapeutic targets for intervention in many diseases.