| OF ORNLP 2413 - I : 1 FEEFEEEE 10.18 11:25 114 11.6 MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS - 1963 ORNL-p-2413 corris : LES SEP 2 2 1966 MASTER MASTER H.C. & LOC; MN,250 LEGAL NOTICE This report ma poapared as an account of Governmeat sponsorod wor', Nolther the Vallad sules, Bor the admission, nor any person acting oa beball of the Commissioa: A. Makes way wuruty or represeautoa, expressed or implied, with respoct to the acci- l'acy, completeness, or us fulatss of the information cooraloed la wais roport, or that the use of any injormation, apparatus, method, procesu disclosed in this roport may not lalringo privately owned righus; or B. Assumos any liabilites will respect to the wes of, or for damages rosuluing from the use of any information, apparatus, actbod, or procons discloud lo this report As used in the above, "per son acting on beba'of the Commission" includes way om- ployee or coninucior of Ibo Commission, or employee of such contractor, to the extent that such employee or contractor of the Commission, or omployee of such contractor prepares, disseminatos, or provides access 10. aay lalormation pursuant to ao employmoat or coalruct with the commission, or his employmert with such contractor. RRIEASED FOR ANNOUNCEMENT IN PJCLEAR SCIENCE ABSTRACTS LONGEVITY AS INFLUENCED BY IRRADIATION IN GERMFREE MICE K. E. Walburg, Jr., G. E. Cosgrove, and A. C. Upton Biology Division, Oak Ridge National Laboratory Oak Ridge, Tennessee Research sponsored by the U. S. Atomic Energy Comnission under contract with the Union Carbide Corporation. To study the effect of the microbial environment on aging, germfree (GF) and conventional (CONV, irradiated and unirradiated mice were examined with respect to their life span and incidence of disease. A non-inbred albino (ICR) and an invred albino (RFM/Unfl strain have been studied to date. Conventional mice were reared with "conventionall' techniques such that the microbial environment was essentially uncontrolled, Germirce mice were raised in rigid isolation inside p..astic film isolators . free of detectable microorganisms. Irradiated mice were either survivors of LD 50/20 experiments receiving 600 to 900R at 12 weeks of age (ICRZ (Walburg et al., 1966) or were exposed to 300 R at 5 to 6 weeks of age (RFM) (Walburg et al., 1965). Unirradiated GF RFM mice had an increased survival rate in the middle one-third of the life span when compared with their CONV counterparts, (Fig. 1) and a similar increase was seen in GF ICR mice F-1 F-1 F-2 when mice dying with cecal volvulus (a disease seen almost exclusively in GF mice) were omitted, (Fig. 2). This difference in survival appears to be associated with infectious diseases of the CONV mice and tends to diminish in the last third of life, so that survivorship is not greatly different in the last decile. In irradiated RFM mice, the GF groups also had greater survival in the middle third of the life span, (Fig. 3) but the differences were largely obscured by the high incidence of leukemia and could be ascribed solely to the absence of myeloid leukemia ia the GF mice. Irradiated GF ICR male mica, however, had considerably less survival in the last two-thirds of the life span than their CONV counterparts. Whether this F-3 & SA . . . 2. II . .. . . difference is ascribable to a specific disease or to an unusually small life-shortening effect of radiation in the CONV grcup is unknown at this time, Irradiation of GF mice resulted in life shortening in both strains. When all causes of death were considered, the longevity was shortened by approximately 125 days in ICR male mice (Fig. 4) and by approximately 300 days in RFM female and 200 days in RFM male mice, (Fig 5). In the F-5 latter strain, early induction of lymphatic leukemia was the primary cause of life shortening, since longevity was reduced by only about 85 days in mice not dying with that disease. The life shortening observed in ICR male mice, however, was not attributable to lyr.phatic leukemia since mice not dying with the disease had as great (or greater) life span reduction as did those dying of all causes. The data suggest that although the absence of detectable micro- bial flora and fauna may alter the form of the survival curve, and may increase the mean age of death, it does not increase the maximum age of death. It is also evident that senescent changes and the life-shortening effect of rediation occur in germfree mice as well as in conventional mice, suggesting that the microbial environnent is not crucial to the development of such phenomena. REFERENCES Walburg, H. E., Jr., Eina I. Mynatt, and D. M. Robie. The effect of strain and diet ou the thirty-day mortality of x-irradiated germfree mice. Radiation Research, 27: 611-629, 1966. Walburg, H. E., Jr., A. C. Uptor, R. L. Tyndall, W. W. Harris, and G. E. Cosgrove. Preliminary observations on spontaneous and radiation-induced leukemia in germfree mice. Proc. Soc. Expt... Biol. and Med 118: 11-14, 1965. ve - War Onninp-2.4.18 LEGENDS FOR FIGURES Fig. I. Mortality of untreated RFM male and female mice us a function of age. ------- Conventional mice, experiment begui, in 1956. -.-.-.- Conventional mice, experiment begun in 1964 (incomplete). to set it as a Germfree mice, experiments begun 1963 and 1964 (incompleto). Number of mice entering experiment in parentheses. Fig. 2. Mortality of untreated ICR mice as a function of age. - Conventional male and female mice. ------- Germfree male and female mice (mice with cecal volvulus omitted). Number of mice entering experiment in parentheses. Fig. 3. Nortality of RFM male and female mice exposed to 300R x-radiation at 5-6 , weeks as a function of age. ------- Conventional mice, experiment begun in 1956. -.-.-.- Conventional inice, experiment begun in 1964 (incomplete). - Germfree mice, experiments begun 1963 and 1964 (incomplete). Number of mice exposed in parentheses. · Fig. 4. Life shortening effect of 650-900R x-radiation administered to germfree ICR male mice, 12 weeks of age. a Mortality from all causes. Mortality with lymphatic leukemia excluded. Fig. 5. Life shortening effect of 300 R x-radiation administered to gormfree RFM male and female mice 5-6 weeks of age. o Mortality from all causes. Mortality with lymphatic leukemia excluded. . - ' P . SE34A . lo; (55) (26) (11) (75) CONV., '56 (52) CONV., '56 CUMULATIVE MORTALITY (%) GF, '64 (84) (32) (15) 20 (102)CONV., '646 (110) CONV., '64- GF., '64 10- 0 100 200 300 400 500 AGE (days) 600 700 800 900 0 100 200 300 400 500 AGE (days) 600 700 800 900 Fig. 1 3 TI 11 3 T . : 904 - CONVENTIONAL (44) GERMFREE (31) (MICE WITH CECAL VOLVULUS OMITTED) CUMULATIVE MORTALITY (%) 0 . 200 400 600 AGE (days) 800 1000 . Fig.2 162 16,319 : . . i Wood (83) CONV., '56 (62) CONV., '36 (87) CONV., '64 CUMULATIVE MORTALITY (%) (95) CONV., '64- GF, '64 (98) 150) (16) GF, '64 0 100 200 300 400 500 AGE (days) 500 760 860 goo Foc zo 360 460 5.0 50 70 800 900 AGE (days) Fig.3 MORTALITY, LYMPHATIC LEUKEMIA EXCLUDED LIFE SHORTENING (days) MORTALITY, ALL CAUSES O or co- -9- 10 o 20 30 40 50 60 70 CUMULATIVE MORTALITY (%) 80 90 100 Fig. 4 1. 16, 320 MORTALITY, ALL CAUSES LIFE SHORTENING (days) no 0 0 - - ------ - MORTALITY, LYMPHATIC LEUKEMIA EXCLUDED · Oorcok 4501 MORTALITY, ALL CAUSES LIFE SHORTENING (days) 11. MORTALITY, LYMPHATIC LEUKEMIA EXCLUDED W or <02 o o o o o do o CUMULATIVE MORTALITY (%) so so do wKLIZ.die.nl Fig.5 2. SKI END - ER * - : . .. - DATE FILMED 11 / 25 / 66 - - . . ". IN. W is W .1 Www MMI