ABSTRACT
These various observations illustrate the fascinating complexity of 5-FU and suggest that most generalizations concerning the specific effects of 5-FU will always be subject to qualifications. They also indicate that efforst to "modulate" the effects of 5-FU, i.e., influence its activity through the use of another agent, are likely to yield different results for different tumors. Nevertheless, the promise of eventually identifying useful 5-FU combinations, including its coincident use with radiation, justify continuing studies on a drug first introduced as many as 30 years ago. The reader is referred to several recent reviews which cover in more detail various aspects of these areas of 5-FU r e s e a r ~ h . ~ . ' ~
The capacity of 5-FU to radiosensitize mammalian cells was first demonstrated by Bagshawl1 and subsequently confirmed by Berry.I2 Their experiments followed the initial observations by Heidelberger's group3 that rodent tumors in vivo were very responsive to the combination of 5-FU and ionizing radiation. Experiments subsequently conducted by Vietti et al.13 using the AKR leukemia system (which is ultrasensitive to 5-FU) confirmed the capacity of the drug to radiosensitize in vivo.
