Proposed models for mechanisms of resistance to HAP (left) and 5-FU (right).

<p>Gene symbols are shown adjacent to the metabolic reactions proposed to be catalyzed by the encoded proteins. Genes that cause drug resistance when overexpressed are shown in <i>blue</i> and activated toxic metabolites of HAP and 5-FU in <i>red</i>. Metabolic reactions are shown as <i>blue</i> arrows, positive regulatory effects in <i>green</i>, and negative regulatory effects in <i>red</i>. For <i>APT2</i>, two possible effects on HAP metabolism are indicated: either inhibition of <i>APT1</i> or catalysis of the opposite reaction, <i>i</i>.<i>e</i>. conversion of HAPMP to HAP. <i>RNR</i> stands for ribonucleotide reductase and <i>TYMS</i> for thymidylate synthase. Not shown in the figure are the effects of overexpressing <i>ADE4</i> and <i>CPA1</i> or <i>CPA2</i>, which boost purine and pyrimidine synthesis, and thus dilute HAP and 5-FU, respectively.