Expression and relationship between topoisomerase I and II a genes in tumor and normal tissues in esophageal, gastric and colon cancers

DNA topoisometases are known to be nuclear enzymes that are important targe ts of topoisomerase I (topo I) and topoisomerase II (topo II) inhibitors in cancel chemotherapy. We investigated the mRNA expression of topo I and lop e II a genes as assessed by northern blot analysis in tumor and the adjacen t normal tissues of esophageal, gastric and colon cancers. The surgical spe cimens consisted of 18 tumor tissues and the adjacent normal tissues includ ing 6 esophageal cancers, 6 gastric cancers and 6 colon cancers. We found t hat the mRNA expression of topo I gene was not significantly different betw een tumor and normal tissues in 18 surgical specimens, whereas the mRNA exp ression of topo II a gene 6 I the all types of tumors was significantly hig her than that of the adjacent normal tissues. Furthermore, the mRNA express ion of rope II a gene in tumor and adjacent normal tissues was correlated w ith the S-phase population in cell cycle. Of great importance was the signi ficant relationship between mRNA expression of topo I and rope II a genes i n tumor and normal tissues was found in esophageal and colon cancers (p<0.0 5), except in gastric cancels. These results indicate that the rationale in tumor specific chemotherapy with rope II inhibitors was based on the findi ng of its higher expression of topo II a gene in tumors than that of normal tissues, art important target of rope II inhibitors, and suggest that the sequential chemotherapy targeting topo I ann topo II enzymes by modulating topo II a expression by topo I inhibitors might be more effective in esopha geal and colon cancers, in terms of their relationship between topo I and t opo II a expression in tumors cells.