Howard J. Curtis

THE ELIMINATION OF CHROMOSOME ABERRATIONS IN LIVER CELLS BY CELL DIVISION.

It was found several years ago (1) that, immediately after a large, single dose of X-rays to young mice, the chromosome aberrations in liver cells increase to become as high as 90 %. Thereafter the percentage decreases slowly over a period of many months to reach control levels after a year or more. The question immediately arose as to why the aberrations declined. The immediate explanation for this was that the cells of the liver normally undergo cell division very rarely, and estimates seemed to indicate that the mitotic rate would be about sufficient to account for the decrease, provided that each aberrant cell died on attempting cell division and was replaced by the division of a normal cell. This explanation was quite satisfying until data became available on mice irradiated with neutrons (2). Here the aberration frequency immediately jumps to very high values and remains as high as the initial values for at least 14 months. If the cell division hypothesis operates for the X-ray case, it surely should operate for the neutron case as well. Since it does not, one is tempted to brand the hypothesis as untenable and look for another. There is, however, a good deal of evidence indicating that cells with aberrant chromosomes are indeed eliminated by cell division. The phenomenon is continually seen in plant cells and in cells in tissue culture. Further, chromosome aberrations increase steadily with age in liver cells (1), whereas in bone marrow cells they do not (3). Since bone marrow cells are certainly as sensitive as liver cells, it seems almost axiomatic that the aberrations in bone marrow cells are eliminated by cell division but that insufficient cell division takes place in liver to eliminate the spontaneously formed aberrations. There is thus an apparent contradiction, and it would seem wise to look for alternative explanations. One such explanation would be that the chromosomes can

Abnormal anaphases in regenerating mouse livers.

The frequency of anaphase abnormalities (usually presented as bridges, bridges plus fragments, or percentage of normal anaphases) is widely used as a criterion of radiation damage in many materials. Here, the frequency of these three abnormal anaphase categories has been studied in a material frequently used for this purpose, regenerating mouse liver, following fast neutron irradiation (50 to 800 rads). A previous study with the plants Tradescantia and barley had shown that detected anaphase bridges increased with dose more or less linearly at first, to a maximum, and then actually declined at higher doses. Two different bridge-loss processes between metaphase and anaphase were shown to account quantitatively for this dose response. The results and conclusions were felt to be applicable to anaphase data in general, from any material. The same response was found here in the mouse liver. The frequency of anaphase bridges per cell increased with dose to a maximum, then declined at larger doses. The percentag...

The Role of Mutations in Liver Tumor Induction in Mice

Liver tumors were induced in mice by neutron irradition followed by a dose of CCl4. The relation between tumor induction and neutron dose was found to be linear at low doses. This is interpreted to...

THE ROLE OF AGE AND X IRRADIATION ON KIDNEY FUNCTION IN THE MOUSE

The demonstration that animals that survive a single dose of irradiation have shorter life spans than their nonirradiated controls (1) has led to the concept of radiation-induced aging. This concept implies that those factors associated with the normal aging process may be advanced or accelerated in the irradiated animals. It has not been demonstrated whether those physiological functions that show an age-dependent decline are accelerated by radiation. Shock (2) and his associates, in studies on the human kidney, have shown that various kidney functions decrease with age. For this reason it was felt that an examination of kidney function in the aging and irradiated mouse might indicate whether there is any similarity in the effects of radiation and aging. The tests employed in this study are the following: (1) the ability of the kidney to concentrate the urine during a 24-hour water fast, (2) the ability of kidney cortex slices to concentrate p-aminohippuric acid against a concentration gradient, (3) the ability of a remaining intact kidney to undergo compensatory hypertrophy after removal of the other, and (4) the ability of the compensating kidney to respond to an anabolic hormone.

Tumor induction as a measure of genetic damage and repair in somatic cells of mice.

CURTIS, H. J., CZERNIK, CAROL, AND TILLEY, JOHN. Repair of Genetic Damage in Somatic Cells of Mice. Radiation Res. 34, 315-319 (1968). Groups of mice were subjected to X-rays and to neutrons, followed either 1 month or 9 months later with a large dose of CC14. The animals were sacrificed at 20 months of age, and liver tumors were scored. The CC14 treatment unmasks the carcinogenic mutations produced by the radiation. It is found that the tumor incidence is about the same for X-rays and neutrons, and that tumor incidence is almost as high when the CC14 is given 9 months postirradiation as when it is given at 1 month. This indicates that, once a carcinogenic mutation is formed, repair is impossible. This is especially interesting, since chromosomal aberrations scored in regenerating liver cells indicate a marked long-term recovery following X-irradiation but not following neutron irradiation. It is concluded that certain structural repair of chromosomes is possible over protracted periods but repair of functional genetic damage probably is not.