Title:Teratogenic Toxicity Evaluation of Bladder Cancer-Specific Oncolytic Adenovirus on Mice
Volume: 21
Issue: 2
关键词:
基因治疗，致畸毒性评估，生物安全性，膀胱癌，溶瘤腺病毒，动物模型。
摘要:
Background: In our previous studies, we had demonstrated the efficiency and specificity
of constructed bladder tissue-specific adenovirus Ad-PSCAE-UPII-E1A-AR (APU-EIA-AR) on
bladder cancer. The virus biodistribution and body toxicity in nude mice have also been investigated.
However, the safety of the bladder cancer-specific oncolytic adenovirus on fetal mice and F1
mice should be under intense investigation.
Objective: In order to evaluate the teratogenic toxicity of bladder cancer-specific oncolytic adenovirus
APU-EIA-AR on mice, in this study, we investigated the fetal mice weight, fetal body
length and tail length, fetal skeleton development, as well as the F1 mice weight, growth curve, and
major organ pathology. These teratogenic toxicity data of bladder tissue-specific adenovirus Ad-PSCAE-
UPII-E1A-AR (AD) would provide safe information prior to embarking on clinical trials.
Methods: On the sixth day of being fertilized, the pregnant mice began to be intramuscularly administrated
with AD (1×107VP, 1×108VP, 1×109VP) every other day for ten days. The pregnant
mice were then divided into two groups. One group was euthanized on the seventeenth day; the fetal
mice were taken out, and the bone structure of the infants was observed. The other group was
observed until natural childbirth. The Filial Generation (F1) is fed for 30 days; the variations in the
growth progress and development were assessed. The mice were then euthanized; The tissues from
major organs were harvested and observed under the microscope.
Results: In the process of teratogenic toxicity test, the Placenta weight, fetal mice weight, body
length, and a tail length of mice fetal in adenovirus treated group did not reveal any alteration.
Meanwhile, comparing with the PBS group, there is no obvious change in the skeleton of fetal
mice treated with adenovirus. During the development process of F1 mice treated with adenovirus,
the changes in mice weight show statistical significance. However, in the progress of the growth
curve, this difference is not very obvious. Furthermore, the pathological section showed no obvious
alteration in major organs.
Conclusion: Our study demonstrated that bladder cancer-specific adenovirus Ad-PSCAE-UPII-
E1A-AR appears safe in pregnant mice without any discernable effects on fetal mice and F1 development.
Hence, it is relatively safe for tumor gene therapy.
