[Therapeutic effect of 5-fluorocytosine on cytosine deaminase gene transduced Wilms' tumor xenograft in nude mice].

OBJECTIVE

To study the effect of 5-fluorocytosine (5-FC) as prodrug in the treatment of Wilms' tumor xenografts transduced with cytosine deaminase (CD) gene.

METHODS

An in vivo model of a poorly differentiated Wilms' tumor transplanted in nude mice was established. Expression adenoviral-vector of CD gene (Ad/CMV-CD) or lac gene (Ad/CMV-lac) was transduced to the tumor xenografts by intratumoral injections. Expression of the transduced genes were confirmed by RT-PCR. Mice with Wilms' tumor xenograft were treated with 5-FC (500 mg.kg-1.d-1 x 10 d). Tumor growth was monitored.

RESULTS

The growth of tumor xenografts transduced with lac gene grew as quick as the untransduced ones. In contrast, the growth of the tumor xenografts transduced with CD gene was significantly inhibited as compared to untransduced and lac gene transduced xenografts. The average rate of inhibition was 65% according to the tumor weight at 8 wk. Cell necrosis was observed in the CD gene transduced tumors.

CONCLUSION

Intratumoral cytosine deaminase gene transduction followed by systemic 5-fluorocytosine is effective in the treatment of Wilms' tumor.