[Safety evaluation of Ad-ASmyc in vitro and in vivo].
OBJECTIVE
To assess the safety of adenovirus-mediated transfer of anti-sense c-myc (Ad-ASmyc).


METHODS
RT-PCR was used to detect the transcription of Ad-ASmyc in HeLa cells infected with extracts from HeLa cells previously infected with Ad-ASmyc. Cell count was used to observe the effects of Ad-ASmyc on the growth of normal human fetal lung diploid cell line 2BS. Ad-ASmyc was given to 2 groups of Balb/c mice by intraperitoneal injection at a dosage of 10(7) pfu and 10(9) pfu respectively. Blood samples were obtained from the mice for liver and renal function tests. PCR was used to screen the vital organs for the presence of adenovirus DNA. Microscopic examination of the vital organs was performed to observe the pathogenicity of Ad-ASmyc.


RESULTS
As a replication-defective virus, Ad-ASmyc could infect 2BS cells effectively, but did not inhibit 2BS cell growth. No mouse died and no signs of general toxicity following intraperitoneal injection of Ad-ASmyc were observed. In mice injected with 10(9) pfu Ad-ASmyc, the adenoviral vector was found in the liver, spleen, kidney, and stomach. On day 6 and day 12 after injection, mild inflammatory infiltration of mononuclear cells was observed.


CONCLUSIONS
The use ofadenoviral vector for antisense c-myc gene transfer in vitro and in vivo is considered to be safe for clinical trial.
Zhang
H
H
Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100021, China.
Lin
C
C
Wei
Y
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D005069:Evaluation Studies as Topic; D005822:Genetic Vectors; D006801:Humans; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000633:toxicity; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc