Project Title: 15. Exposure to External and Internal Radiation Evaluation of Hazards from Tritium--Dominant Lethal Mutations in Mice RX-O01-01-(c) Relationship to Other Projects: This work is closely related to the present studies by the late Dr. Gonzalez of Columbia University and BNL on the genetic effects of radiation in Drosophila melanogaster. At ORNL, W. Russell, L, Russell, and E. Oakburg are currently determining the incidence of recessive mutations from exposure to tritium. M. Lyon at M,R,C., Radiobiology Research Unit, Harwell, England, and A. C, Bateman, Christie Hospital and Holt Radium Institute, Manchester, England, have been working on the radiation induction of dominant Lethal mutations in rodents, 16, Technical Progress in FY 1973: a ; A total of 1,780 female animals have been bred. tritium and bred with males on tritium, o~ These included 748 on 335 bred to males on regular water, 336 on normal water bred to males on tritiated water, and 361 control animals where both partners were on normal water. Of the 1,780 animals, 1,017 became pregnant and 10,904 corpora lutea were counted. While these figures repre- sent a rather significant number of animals, indications are if a genetic effect does exist, it is not great enough to be readily apparent, Computer programs are currently being written to enable a detailed examination of the data available. Animals were examined for incorporation of tritium for as long as 302 days after initiation of the experiment. Preliminary results indicate that by 14 days after beginning on tritium water, the plasma and wet tissue tritium activity has reached more than 80% of the values measured at 302 days. The dry tissue activity similarly plateaus within the first 30 days on tritiated H,0. After maintenance on tritium for 37 weeks, animals have been sacrificed, the bone marrow harvested from the hind legs, and evaluated for stem cell Initial results indicated content as measured by the spleen colony technique. a reduction in stem cell number in the tritiated animals. A pilot determination is now in progress aimed at measuring the amount of tritium incorporated into DNA,RNA, histone and residual chromosome associated with protein. As yet this work is too preliminary for comment, however, the teghniques were standardized. 17. Wepected Results in FY 1974: Accumulation of information on the long-term incorporation of tritiated water into the various body compartments and nuclear constituents will con- tinue in order to determine whether or not maintenance on 100 x the MPC will (See Continuation Sheet) L11918b RX - 26