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Radiation Hazard Research Group,
National Institute of Radiological Sciences, Chiba 263-8555,
Japan.
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Division of Biology and Oncology, National
Institute of Radiological Sciences, Chiba, Japan.
The host-defense mechanisms against cancers
are known to be modulated by changing the environmental
factor(s). The spontaneous incidence of myeloid leukemia
is about 1% in C3H/He mice, and the incidence increases
up to 23.3% when a single dose of radiation, 3 Gy X-ray,
is exposed to a whole-body. Since calorie restriction
was known to reduce the incidence of spontaneous tumors,
a question as to whether such radiation induced-increase
of myeloid leukemia would be also decreased by calorie
restriction, was aimed to answer to elucidate possible
mechanism of radiation-induced myeloid leukemia. By the
calorie restriction, the incidence of myeloid leukemia
was significantly decreased. In addition, the latent period
of the myeloid leukemia in the groups for calorie restriction
was significantly extended at a greater extent as compared
with the control diet groups. Number of hemopoietic stem
cells, the possible target cells for radiation-induced
leukemias, in the groups for the calorie restriction demonstrated
a significant decrease, especially in the spleen, as compared
with that in the control, when the evaluation was made
at the time of radiation exposure.
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Division of Biology and Oncology,
National Institute of Radiological Sciences, Inage-ku, Chiba,
Japan.
Dietary restriction, especially caloric
restriction, is a major modifier in experimental carcinogenesis
and is known to decrease significantly the incidence of
neoplasms. Gross and Dreyfuss [Gross, L. & Dreyfuss,
Y. (1984) Proc. Natl. Acad. Sci. USA 81, 7596-7598; Gross,
L. & Dreyfuss, Y. (1986) Proc. Natl. Acad. Sci. USA
83, 7928-7931] reported that a 36% restriction in caloric
intake dramatically decreased the radiation-induced solid
tumors and/or leukemias. Their protocol predominantly
produced lymphatic neoplasms. It is of interest to observe
the effect of caloric restriction on radiation-induced
myeloid leukemia, because the disease was observed to
have been increased in the survivors of the atomic bombs
in Hiroshima and Nagasaki. The spontaneous incidence of
myeloid leukemia in C3H/He male mice is 1%, and the incidence
increased to 23.3% when 3 Gy of whole-body x-ray irradiation
was given. However, the incidence of myeloid leukemia
was found to be significantly decreased by caloric restriction;
it was reduced to 7.9% and 10.7% when restriction was
started before (6 weeks old) and after (10 weeks old)
irradiation, respectively. In addition, the onset of the
myeloid leukemia in both restricted groups was prolonged
to a greater extent as compared with the control diet
group. Caloric restriction demonstrated a significant
prolongation of the life span in the groups on a restricted
diet after having been exposed to irradiation, either
before or after dietary restriction, in comparison with
mice that were only irradiated.
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The effect of 1 to 6 weeks' adaptation
to intermittent fasting (alternating periods of 24 h fasting
and subsequent 24 h feeding) on the manifestations of
radioresistance of mice subjected to whole-body gamma-irradiation
was studied. A favourable effect of this feeding regimen
on the survival of irradiated animals was observed. The
optimal radioprotective effect was achieved in mice adapted
to intermittent fasting for 2 to 3 weeks and irradiated
after 24 h of food intake. Furthermore, it was shown that
the radioresistance of the adapted organism depends on
the momentary state of food intake. After renewal of the
normal ad libitum feeding the adaptively induced radioresistance
decreases.
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