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Publication : Analysis of tumors arising in male B6C3F1 mice with and without AAV vector delivery to liver.

First Author  Bell P Year  2006
Journal  Mol Ther Volume  14
Issue  1 Pages  34-44
PubMed ID  16682254 Mgi Jnum  J:115067
Mgi Id  MGI:3690606 Doi  10.1016/j.ymthe.2006.03.008
Citation  Bell P, et al. (2006) Analysis of tumors arising in male B6C3F1 mice with and without AAV vector delivery to liver. Mol Ther 14(1):34-44
abstractText  The present study reports on the frequency of liver tumors observed in a gene therapy study with AAV vectors in male mice of the B6C3F1 hybrid background, which are known to have a high frequency of spontaneous liver tumors. Male mice with mutations in their Otc gene and their wild-type siblings received AAV vectors expressing either the murine Otc or the LacZ gene. Untreated control animals were included in the study. All experimental groups, including wild-type and OTC-deficient animals not treated with vector, developed liver nodules, which in some cases were due to hepatocellular carcinoma. Vector DNA was lower in tumors than in adjacent normal liver. A statistical analysis of the data did not show an association between treatment with Otc vectors and formation of tumors in OTC-deficient mice. However, mice treated with LacZ vectors showed increased risks of tumor formation and hepatocellular carcinoma relative to untreated animals or animals that had received vectors with Otc as the transgene. It appears that AAV vectors alone do not contribute to the formation of tumors in these strains of mice although the expression of LacZ alone or in combination with vector may be problematic.
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