Detailed data that would permit the construction of orientation charts, e.g., text-figures 3 to 5, for the Friend virus (32) have not been published, but it is among the most rapidly acting tumor viruses and is comparable to those of Rous sarcoma and Shope papilloma. Pilot screening studies involving the Friend leukemia have been carried out by Suguira, and are to be reported by him in a paper now in press (Gann, September, 1959). The following information, including the summary of results contained in table 4, was kindly supplied by Dr. Suguira.6

Table 4. Eight Compounds Among Over 200 Tested Which Showed The Ability To Inhibit Friend Virus Leukemia (Suguira)

1. Mitomycin c

2. Triethylenemelamine (TEM)

3. Thioguanine

4. Methanesulfonic acid, tetramethylene ester (Myleran)

5. Estradiol

6. Methoxyn

7. Methanesulfonic acid, nonamethylene ester [l,9-Di(methanesulfonoxy)nonane]

8. 9 α-Fluoro-2-o-methylhydrocortisone acetate

The 8 compounds listed in table 4 were those found to be effective among over 200 compounds examined in preliminary therapeutic tests in which the administration of candidate compounds was initiated 24 hours after the inoculation of mice with Friend leukemia virus. The criterion of antitumor activity was the ratio of the weights of spleens of the treated animals to those of controls, 2 weeks after the inoculation of virus. Four of the compounds that were found to be the most effective in this preliminary test (#1, 2, 4, and 7 of table 4) were subjected to follow-up tests in which the administration of the compounds was delayed until 5 days after virus inoculation. Neoplastic cells can be detected by microscopic examination of the spleens of control inoculated mice at this time. All 4 compounds were also effective by the more severe therapeutic test. In some cases the spleens of treated mice weighed less than 0.2 gm. and could not be differentiated from the normal spleens of uninoculated mice, whereas the spleens of the inoculated controls were greatly enlarged and weighed from 2 to 4 gm. at the termination of the test. Again, the compounds that were effective in this viral-tumor screening system were among those that have been found to be most effective in other systems.

Other Tumor Virus-Host Systems

The detailed biological information necessary for the planning and carrying out of chemotherapeutic research is also available for 3 additional tumor virus-host systems: the virus-induced fowl leukoses, myeloblastosis (33), erythroblastosis (34), and lymphomatosis (35). However, systematic studies have not yet been made on the potential value of these systems as chemotherapeutic tools.

Concluding Comments

Sufficient knowledge of the biological properties of several well-established tumor virus-host systems has now been achieved to permit them to be used in systematic chemotherapeutic research. Pilot studies by Groupe and Johnson and their associates on the Rous sarcoma virus, and by Suguira on the Friend leukemia virus, indicate that highly efficient, reproducible, prophylactic, and therapeutic tests can be carried out with both of these systems under practical conditions. The screening methods in both systems were capable of distinguishing several of the chemotherapeutic compounds which previously had been found to be among the most effective in other nonviral tumor test systems.

These findings should lend encouragement to a full-scale test program involving viral tumors, in the further search for more effective antitumor agents.