Evaluation of biodistribution and safety of adenovirus vector containing MDR1 in mice.
BACKGROUND
The aim of this study is to examine the safety and distribution of Ad-EGFP-MDR1, an adenovirus encoding human multidurg resistance gene (human MDR1), in the mice colon carcinoma model.


METHODS
After bone marrow cells (BMCs) were infected with Ad-EGFP-MDR1, they were administered by intra bone marrow-bone marrow transplantation (IBM-BMT). Total adenovirus antibody and serum adenovirus neutralizing factor (SNF) were determined. Biodistribution of Ad-EGFP-MDR1 was detected by in situ hybridization and immunohistochemistry. The peripheral hematocyte white blood cell (WBC), haemoglobin (Hb), red blood cell (RBC) and platelet (Plt) counts were analyzed.


RESULTS
Neither total adenovirus antibody nor SNF increased weeks after BMT. In situ hybridization and immunohistochemistry demonstrated concordant expression of human MDR1 and P-gp which were found in lung, intestine, kidney and BMCs after BMT, but not detected in liver, spleen, brain and tumor. No significant abnormality of the recovery hematocyte was observed on Day 30 after treatment.


CONCLUSIONS
The results indicate that IBM-BMT administration of a replication defective adenovirus is a feasible mode of delivery, allowing exogenous transference. The findings in this study are conducted for the future long-term studies of safety assessment of Ad-EGFP-MDR1.
Zhao
ZhenZhen
Z
Surgery and Oncology Laboratory, Pediatric Research Institution, Children's Hospital of ChongQing Medical University, ChongQing, China.
Liu
Wei
W
Su
Yuxi
Y
Zhu
Jin
J
Zheng
GaiHuan
G
Luo
Qing
Q
Jin
XianQing
X
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000379:methods; D045744:Cell Line, Tumor; D003673:Defective Viruses / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014162:Transfection
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000914:Antibodies, Viral