the host genome and altering the regulation of host cell proto-oncogenes. This 
event occurs with a much lower efficiency so that malignancy develops over a 
longer period of time. 
The Moloney MuLV that is the backbone of our vector belongs to the slowly 
transforming retrovirus class and there is no evidence that the SAX vector has 
acutely transforming properties. Moloney MuLV is known to cause T cell 
lymphomas in rodents. 
The mechanism by which slowly transforming retroviruses cause 
transformation has recently been reviewed (Nosse. 1986). Fig. 2 (Appendix A) 
Illustrates some of the mechanisms by which transformation can occur. The first 
mechanism depicts insertion of a viral LTR promoter 5' to the proto-oncogene 
with increased transcription resulting In malignant transformation. Mutation 
of the viral genome would probably need to occur since transcriptional overlap 
Interference (Cullen et al.. 1984) reduces transcription from the 3' LTR. 
Primarily where an LTR is deleted or a transcriptional termination signal is 
Inserted between the two LTR's will promoter Insertion act as a mechanism for 
Insertional mutagenesis. Therefore, the frequency with which transformation 
will occur by promoter insertion is dependent on both insertion within the 
appropriate sequence and mutation of the inserted viral genome. The second 
mechanism is transcriptional enhancement of the proto-oncogene through the LTR 
enhancer. In this case, the virus can integrate 5' or 3' to the proto- 
oncogene. The third and fourth mechanisms show insertion of the virus 
within an exon so that viral protein sequences are combined with the endogenous 
sequence. 
Transformation by Moloney MuLV resulting in murine T cell lymphomas has 
been associated with insertion near the pim-1 domain in approximately 502 of 
the lymphomas studied (Cuypers et al . , 1984). The mechanism appears to be by 
Recombinant DNA Research, Volume 12 
[ 57 ] 
