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Updated: Nov 25, 2025
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Teratogenic Toxicity Evaluation of Bladder Cancer-Specific Oncolytic Adenovirus on Mice
Keqing Lu1, Fang Wang2, Baoliang Ma1
1Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University), Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou730000, China.
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.
Insights
This study found that the bladder cancer-specific oncolytic adenovirus Ad-PSCAE-UPII-E1A-AR (AD) is safe for pregnant mice. It showed no adverse effects on fetal development or F1 generation growth, supporting its use in tumor gene therapy.
Area of Science:
- Oncolytic virotherapy
- Cancer gene therapy
- Toxicology
Background:
- Previous studies confirmed the efficacy and specificity of bladder tissue-specific adenovirus Ad-PSCAE-UPII-E1A-AR (APU-EIA-AR) for bladder cancer treatment.
- Biodistribution and general toxicity in nude mice were previously assessed.
- The safety of this oncolytic adenovirus on fetal and F1 generation mice requires thorough investigation before clinical application.
Purpose of the Study:
- To evaluate the teratogenic toxicity of the bladder cancer-specific oncolytic adenovirus APU-EIA-AR in mice.
- To assess the impact of the adenovirus on fetal development, including weight, body length, tail length, and skeletal structure.
- To examine the effects on the F1 generation's weight, growth curve, and major organ pathology.
Main Methods:
- Pregnant mice were administered the adenovirus (AD) intramuscularly on gestation day 6, every other day for ten days.
- Fetal mice were examined on gestation day 17 for teratogenic effects, including skeletal development.
- The F1 generation was observed for 30 days post-birth to assess growth and organ pathology.
Main Results:
- No significant alterations were observed in placenta weight, fetal mice weight, body length, or tail length in the adenovirus-treated groups compared to controls.
- Fetal mice skeletal development showed no obvious changes after adenovirus treatment.
- While F1 mice weight changes were statistically significant, the growth curve differences were not pronounced, and major organ pathology was absent.
Conclusions:
- The bladder cancer-specific adenovirus Ad-PSCAE-UPII-E1A-AR demonstrates safety in pregnant mice, with no discernible adverse effects on fetal development or the F1 generation.
- These findings provide crucial safety data for the potential clinical application of this oncolytic adenovirus in bladder cancer therapy.
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