‘I Project Title: 16. Molecular and Cellular Radiobiology Storage and Transfer of the Genetic Message Technical Progress in PY 1973: RX-03-02-(d) (Cont'd.) but does not have the high virulence of WEE, EEE, and VEE. SFV is therefore of interest as a potential cause of human disease, and as a relatively safe laboratory model for the virulent Equine encephalitis virus infections which are of immediate economic concern in veterinary medicine and a perennial threat Co man. The results of further experiments with polynucleotides against SFV infection in mice were in excellent agreement with earlier results. Mice which were treated with 100 peg of poly(rierC) or 100 wg poly(rA-rU) 2-4 hr before ip injection of SFV were usually protected, whether treatment was continued or not, Thus a single prophylactic injection of 100 wg poly(rI-rC) gave complete protection 0/35 deaths, a single injection of 10 wg gave 1/40 deaths. As noted previously, most mice given SFV ic died of the infection, ‘but those protected lived slightly longer than those in untreated groups. Mice which survived as a result of poly(rlIerC) treatment were challenged with a second injection of SFV ip 6 weeks after the first dose to determine whether they had developed immunity as a result of the earlier exposure to the virus, the two experiments completed so far, mice which had previously received SFV and poly (ri-rC) had a lower mortality than did control mice, These challenging data are being followed up, In Complexes of poly(ri-rC) and histone and of poly(riIerC) and polylysine or polyarginine had antiviral activity against SFV infection in mice but from the preliminary data it is not yet possible to say whether this was enhanced compared with the activity of poly(rIerC) alone, These studies are continuing. In collaboration with Drs. F. M, Schabel, H. E, Skipper and W. R, . Laster (Kettering-Meyer Laboratories, Southern Research Institute, Birmingham, Alabama), poly(rIerC) and poly(rA»srU) were tested as prophylactic agents against spontaneous AKR lymphoma in AKR mice, AKR mice were selected that were approximately 6 months of age, but free of grossly apparent clinical lymphoma at the time treatment was begun; i.e,., animals had no grossly discernible enlarged thymus, spleen or peripheral lymph nodes, After treat- ment with poly(rI-rC) or poly(rA-rU), there was no significant change in the cumulative mortality pattern, There were no differences in the numbers of mice in control and treated groups dying without gross signs of disease, Treatment given before the development of frank clinical signs of leukemia or lymphoma in AKR mice can, in fact, abort the development of the disease, Thus in mice treated with palm O-ara-C at 5 mg/kg, treated once a day for 7 daymy then rested for 7 days, then treated for 7 days, then rested for 7 days,-@fc., from 6-12 months of age, treatment beginning at 180th day of life Shere was about a 40% disease-free survivor rate, compared to about a 10% survivor rate in untreated control animals, The data collected so far fail to indicate that, at the doses and schedules used, either poly(riIerC) or poly(rAerU) had any influence on the subsequent development of clinically (See Continuation Sheet) bP T9431b RX - 256