y g 3 Studies Using the H5.0 1 ORSVTK Vector in Animal Models of Human Mesothelioma 
Animal Models of Human Mesothelioma Have Been Developed, (see Appendix A-Smythe et al. 
1 994a) : Both a subcutaneous flank tumor model and an intraperitoneal model of mesothelioma 
have been developed in Severe Combined Immunodeficient (SCID) mice by injection of 1-45 and 
REN cells (Smythe et al., 1994a). In the flank tumor model, 5-10 million cells in log phase 
growth are injected subcutaneously. 
Measurable tumors grow in a reproducible fashion 
(see below). In the intraperitoneal model, 30 to 60 
million REN or 1-45 cells are injected into the 
peritoneal cavities of SCID mice. Within 7-10 days, 
tumor nodules are noted on peritoneal surfaces. By 
30 days large tumor deposits are present-most 
notably in the small bowel mesentery, lesser 
omentum, splenic hilar area, and biliary tree (see 
Appendix C and Fig. 1 -panels A, C, E- arrows). 
Uniform death of animals is noted at 5-7 weeks, 
usually due to biliary or bowel obstruction. We have 
chosen the intraperitoneal rather than pleural model 
since it is extremely difficult to introduce cells into 
the pleural cavity of mice without causing death due 
to bilateral pneumothorax (the two pleural cavities 
are in communication). Since 20% of mesotheliomas 
arise from the peritoneum, we feel this model is 
appropriate and will allow easy extrapolation to the 
pleural cavity. 
Figure 1 
We have also developed a rat pleural model of mesothelioma by injection of a rat 
mesothelioma cell line (11-45- provided by Dr. Cheryl Walker, M.D. Anderson Cancer 
Institute) that was derived from asbestos exposed Fisher rats. Injection of one million 
cells into the pleural cavity of Fisher rats results in a rapidly growing tumor that encases 
the thoracic organs and leads to death in 20-25 days (see Fig. 2, below). Panel A shows the 
thoracic cavity of a rat injected with tumor two weeks previously showing massive tumor 
growth and throughout the thorax. The head of the animal is at the top of the Figure. The 
heart has been removed. The right lung (RL) and left lung (LL-arrowhead) are visible 
but encased in tumor (tu-arrows). There are nodules of tumor on the chest wall (cw) and 
throughout the mediastinum. Panel B shows a close-up of the chest wall of another rat. 
There are many tumor nodules (tu- arrows) surrounding the lung (L) and on the chest 
wall (cw). 
Fig. 2 
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Recombinant DNA Research, Volume 20 
