[Study on the in vivo killing activity of YCD/5-FC gene therapy system on K562B cells].
OBJECTIVE
To elucidate the killing activity of yeast cytosine deaminase/5-fluorocytosine (YCD/5-FC) gene therapy system on gene-transferred tumorigenic cell line K562B in vivo.


METHODS
K562B cell was infected with high titer virus and a gene transferred cell clone, YCD-K562B, was selected. Twelve male SCID mice of 4 week old were divided into 2 groups at random and both YCD-K562B and K562B cells were implanted to each mice. 5-FC or saline was given i. p for 10 days after tumor developed, and relative tumor volume was measured every 3 days. At the end of experiment, animals were sacrificed and the specimens were processed for histopathological examination.


RESULTS
At the end of experiment (21 days after tumor cell implantation), the relative tumor volume of the 4 groups were: YCD-K562B + 5-FC 2.922 +/- 0.581, YCD-K562B + saline 24.434 +/- 4.790, K562B + 5-FC 22.701 +/- 2.350 and K562B + saline 24.460 +/- 1.670; t-test analysis showed that 5-FC could kill cells (YCD-K562B) in vivo (P = 0.0001), but had no effect on the growth of gene-untransferred cells (K562B) (P = 0.096). In YCD-K562B + 5-FC group, relative tumor volume reduced in 3 approximately 6 days after treatment (the minimum was 0.681). Necrosis around artery could be found in the tumor of YCD-K562B + 5-FC group.


CONCLUSIONS
YCD/5-FC suicide gene therapy system has a significant in vivo killing activity to gene-transferred tumorigenic YCD-K562B cell.
Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Yusheng
Y
Zhang
Jianmin
J
Wang
Hong
H
Zhou
Yongping
Y
Zhai
D000818:Animals; D043525:Cytosine Deaminase; D005437:Flucytosine / Q000378:metabolism / Q000494:pharmacology*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020014:K562 Cells; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000628:therapy*; D009700:Nucleoside Deaminases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D014162:Transfection; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase