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Teratogenic Toxicity Evaluation of Bladder Cancer-Specific Oncolytic Adenovirus on Mice

Author(s):

Keqing Lu, Fang Wang*, Baoliang Ma, Wenjuan Cao, Qi Guo, Hanzhang Wang, Ronald Rodriguez and Zhiping Wang*   Pages 1 - 7 ( 7 )

Abstract:


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, we also investigated the virus biodistribution and body toxicity in nude mice. However, the safety of the bladder cancer specific oncolytic adenovirus on fetal mice and F1 mice should be under intense investigation.

Objectives: 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 AdPSCAE-UPII-E1A-AR (AD) would provide safe information prior to embarking on clinical trials.

Methods: At sixth day of being fertilized, the pregnant mice began to be intramuscular administrated with AD (1×107VP, 1×108VP, 1×109VP) every other day for ten days. Then ,the pregnants were devided into two groups. One group was euthanized at seventeenth day, took out the fetal mice ,observing the bone structure of the infants. The oth er group was observed until natural childbirth. The Filial Generation (F1) are feeded and growth for 30 days, the variation in the growth progress and developmen t were assessed. Then the mice were euthenazied, the organ tissue were performed pathological section and HE staining, observing the changes under microscope.

Results: In the process of teratogenic toxicity test , comparing with control group ,the Placenta weight ,fetal mice weight , body len gth and tail length of mice fetal in adenovirus treated group did not reveal any alteration. Comparing with PBS group, there is no obvious change in skeleton of fetal mice treated with adenovirus. During the development process of F1 mice treated with adenovirus, the changes of mice weight show statistical significance. Howerer, in the progress of 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 appear safe in the pregnant mice without any discernable effects on fetal mice and F1 development. Hence, It is a relatively safe for tumor gene therapy.

Keywords:

Gene therapy, Teratogenic Toxicity Evaluation, Biosafety, Bladder Cancer, Oncolytic Adenovirus

Affiliation:

Gansu Nephro-Urological Clinical Center; Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University); Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou, Center of Medical Experiments, School of Basic Medical Sciences, Lanzhou University, Gansu Province, Lanzhou, Gansu Nephro-Urological Clinical Center; Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University); Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou, Gansu Nephro-Urological Clinical Center; Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University); Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou, Gansu Nephro-Urological Clinical Center; Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University); Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou, Department of Urology, The University of Texas Health Science Center at Sa n Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, Department of Urology, The University of Texas Health Science Center at Sa n Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, Gansu Nephro-Urological Clinical Center; Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University); Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou



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