The dog (C874) which died 3 years after transplantation of transduced marrow 
cells showed at autopsy a prostatic tumor which infiltrated the urinary bladder 
and occluded the trigone of the bladder, thus leading to severe bilateral 
hydronephrosis and death secondary to uremia. On 1-3-92, 3 days before the 
death, serum creatinine was 10.2 mg/dl (normal 0.6- 1.0 mg/dl) and serum urea 
nitrogen was 70 mg/dl (normal 6-30 mg/dl). Tumor metastases were found in 
liver, lungs and mesentery. Histology showed an adenocarcinoma of the prostate. 
Multiple samples from normal and tumor tissue were analyzed for the presence 
of retrovirus vector DNA by PCR amplification of neo gene sequences. Vector 
DNA was detected only in peripheral blood granulocytes (Figures 4a and b). 
None of the tumor samples contained retrovirus vector DNA. 
Samples from normal and tumor tissue were also analyzed for the presence of 
replication-competent amphotropic proviral genomes by PCR amplification of 
amphotropic envelope gene sequences. No replication-competent proviral 
genome was detected. It is therefore unlikely that tumor development was 
related to gene transduction into transplanted marrow cells. Tumor development 
is most likely a late side effect of high-dose TBI used for myeloablation before 
infusion of transduced marrow cells. Observations in dogs have shown that TBI 
significantly increases the relative risk of developing a malignancy (33,34). 
Similar observations have been reported in Rhesus monkeys (35) and in human 
beings (36). Prostatic carcinoma is a rare malignancy in normal dogs. In our 
laboratory, 1 of 44 otherwise normal dogs which developed a malignancy, was 
diagnosed to have a prostatic carcinoma. After TBI 1 of 11 irradiated dogs which 
developed a malignant tumor showed an adenocarcinoma of the prostate. 
One dog (D425) died on day 84 after transplantation of transduced peripheral 
blood cells from chronic canine distemper sclerosing encephalitis. On day 70, the 
dog was found to have convulsions and fever up to 104°F. Serum chemistry was 
normal except for a mildly increased glucose of 140 mg/dl (normal 31-109 mg/dl) 
and a slightly decreased phosphorus of 3.8 mg/dl (normal 4.0-9.2 mg/dl). The 
animal was treated empirically with a broad-spectrum antibiotic (Tazidime) as 
well as with phenytoin and diazepam for control of convulsions. The temperature 
decreased to 101°F and the convulsions disappeared. On day 81, the dog started 
biting, developed seizures, and became increasingly unaware of its surroundings. 
Serum chemistry on day 83 was completely normal including glucose and 
phosphorus. Due to its poor condition, the dog was euthanized on day 84 with 
pentobarbital. Autopsy did not show any macroscopic abnormalities. 
Histological examination of the brain revealed a subacute, multifocal sclerosing 
encephalitis which was most severe in the lateral and medial ventral frontal 
cortex, somewhat less severe in the inferior temporal cortex, and least severe in 
the thalamus. The lesions were characterized by marked lymphocytic 
perivascular cuffing, focal gliosis and an extensive invasion of the brain 
parenchyma with monoclonal cells, and foci of demyelination. Stains for bacteria, 
fungi, acid fast organisms and nocardia were negative. No viral inclusion bodies 
were seen in the brain sections; however, one to two inclusion bodies were seen 
in the renal pelvis epithelial cells. These lesions are compatible with chronic viral 
canine distemper. This form of distemper encephalitis represents a slow viral 
Recombinant DNA Research, Volume 18 
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