Page 410 - 2014 Printable Abstract Book
P. 410
(PS7-57) Analysis of role of calorie restriction in prevention of spontaneous and radiation-induced
carcinogenesis using mathematical multistage carcinogenesis model. Shusuke Tani; Yi Shang; Sizuko
Kakinuma; Takamitsu Morioka; Toshiaki Kokubo; and Yoshiya Shimada, National Institute of Radiological
Sciences, Chiba, Japan
Calorie restriction (CR) is repeatedly reported to extend mean and maximum life span in a variety
of species. It also suppresses the tumor development, which occurs not only spontaneously but also is
induced by chemicals and radiation. The molecular and cellular mechanisms of cancer prevention in CR
have been studied intensively. In this study, we evaluated mathematically the effect of CR on cancer risk
using Armitage-Doll model. The data we utilized are those conducted in our laboratory (Shang et al. 2014);
male B6C3F1 mice were irradiated with 3.8 Gy of X rays or non-irradiated at neonate (one week after
birth), treated with CR (65 kcal/week/mouse, about 30% calorie reduction compared to 95
kcal/week/mouse) from 7 weeks of age and observed through lifespan. Armitage-Doll model has been
utilized to estimate the parameters of multi-stage carcinogenesis of each organ. Based on the slope and
intercept in double logarithmic graph of the model, it is possible to estimate the number of stages up until
full malignancy and the product of the probabilities of the transformation from (r−1) th cell to r th cell. In
spontaneous hepatocarcinogenesis, the number of stages was 3.9 in non-CR group and 7.2 in CR group,
indicating that higher calorie load (95 kcal/week/mouse) has an ability to facilitate 3.3 stages of
hepatocarcinogenesis. The number of stages was 2.8 in non-CR group and 5.1 in CR group in radiation-
induced hepatocarcinogenesis. The number of stages of spontaneous lung adenocarcinoma in CR group
also increased compared to that in non-CR group (7.4 in CR group and 4.3 in non-CR group). On the other
hand, in radiation-induced Harderian tumorigenesis, the number of stage remained unchanged (3.5 in
non-CR group and 3.7 in CR group). But, the intercept of Harderian tumor graph in CR group was about
1/10 of that in non-CR group, indicating that higher calorie load accelerated the speed to accumulate
mutations within a cell although it did not change the stages for carcinogenesis. It is suggested not only
that CR changes the number of stages for carcinogenesis but also that the (r−1) th cells transform to r th
cells easier in high calorie condition. Therefore, the mechanism of cancer prevention in CR is different in
an organ specific manner.
(PS7-58) Association of radiation-induced genes with chronic non-cancer diseases in mayak workers
1
2
occupationally exposed to prolonged radiation. Michael Abend, Prof. Dr. ; Tamara Azizova, Dr. ; Müller
1
1
1
2
3
Kerstin, Dr. ; Harald Dörr, Dr. ; Sven Senf ; Helmut Kreppel, Prof. Dr. ; Galina Rusinova, Dr. ; Natalia
4
2
1
4
Vyazovskaya, Dr. ; Kristian Unger, Dr. ; Herbert Braselmann, Dr. ; and Viktor Meineke, Prof. Dr.
1
Bundeswehr Institute of Radiobiology, Munich, Germany ; Southern Urals Biophysics Institute (SUBI),
3
2
Ozyorsk, Russian Federation ; Bundeswehr Medical Office, Department IX 1, Munich, Germany ; and
4
Research Unit of Radiation Cytogenetics, Integrative Biology Group, Helmholtz Center, Munich, Germany
We examined the association of chronic diseases other than cancer with gene expression altered
after occupational chronic exposure in Mayak workers. Workers were exposed to combined incorporated
239Pu and external gamma-rays (n=82) or to external gamma-rays only (n=18) and 50 unexposed
individuals served as controls. Peripheral blood was taken, RNA was isolated, converted into cDNA and
stored at -20°C. In previous analysis we screened the whole genome for radiation-associated candidate
genes and validated 15 mRNAs and 15 microRNAs using qRT-PCR. Within this analysis we examined the
association of these genes with 15 different chronic diseases. We examined the radiation-gene-disease
carcinogenesis using mathematical multistage carcinogenesis model. Shusuke Tani; Yi Shang; Sizuko
Kakinuma; Takamitsu Morioka; Toshiaki Kokubo; and Yoshiya Shimada, National Institute of Radiological
Sciences, Chiba, Japan
Calorie restriction (CR) is repeatedly reported to extend mean and maximum life span in a variety
of species. It also suppresses the tumor development, which occurs not only spontaneously but also is
induced by chemicals and radiation. The molecular and cellular mechanisms of cancer prevention in CR
have been studied intensively. In this study, we evaluated mathematically the effect of CR on cancer risk
using Armitage-Doll model. The data we utilized are those conducted in our laboratory (Shang et al. 2014);
male B6C3F1 mice were irradiated with 3.8 Gy of X rays or non-irradiated at neonate (one week after
birth), treated with CR (65 kcal/week/mouse, about 30% calorie reduction compared to 95
kcal/week/mouse) from 7 weeks of age and observed through lifespan. Armitage-Doll model has been
utilized to estimate the parameters of multi-stage carcinogenesis of each organ. Based on the slope and
intercept in double logarithmic graph of the model, it is possible to estimate the number of stages up until
full malignancy and the product of the probabilities of the transformation from (r−1) th cell to r th cell. In
spontaneous hepatocarcinogenesis, the number of stages was 3.9 in non-CR group and 7.2 in CR group,
indicating that higher calorie load (95 kcal/week/mouse) has an ability to facilitate 3.3 stages of
hepatocarcinogenesis. The number of stages was 2.8 in non-CR group and 5.1 in CR group in radiation-
induced hepatocarcinogenesis. The number of stages of spontaneous lung adenocarcinoma in CR group
also increased compared to that in non-CR group (7.4 in CR group and 4.3 in non-CR group). On the other
hand, in radiation-induced Harderian tumorigenesis, the number of stage remained unchanged (3.5 in
non-CR group and 3.7 in CR group). But, the intercept of Harderian tumor graph in CR group was about
1/10 of that in non-CR group, indicating that higher calorie load accelerated the speed to accumulate
mutations within a cell although it did not change the stages for carcinogenesis. It is suggested not only
that CR changes the number of stages for carcinogenesis but also that the (r−1) th cells transform to r th
cells easier in high calorie condition. Therefore, the mechanism of cancer prevention in CR is different in
an organ specific manner.
(PS7-58) Association of radiation-induced genes with chronic non-cancer diseases in mayak workers
1
2
occupationally exposed to prolonged radiation. Michael Abend, Prof. Dr. ; Tamara Azizova, Dr. ; Müller
1
1
1
2
3
Kerstin, Dr. ; Harald Dörr, Dr. ; Sven Senf ; Helmut Kreppel, Prof. Dr. ; Galina Rusinova, Dr. ; Natalia
4
2
1
4
Vyazovskaya, Dr. ; Kristian Unger, Dr. ; Herbert Braselmann, Dr. ; and Viktor Meineke, Prof. Dr.
1
Bundeswehr Institute of Radiobiology, Munich, Germany ; Southern Urals Biophysics Institute (SUBI),
3
2
Ozyorsk, Russian Federation ; Bundeswehr Medical Office, Department IX 1, Munich, Germany ; and
4
Research Unit of Radiation Cytogenetics, Integrative Biology Group, Helmholtz Center, Munich, Germany
We examined the association of chronic diseases other than cancer with gene expression altered
after occupational chronic exposure in Mayak workers. Workers were exposed to combined incorporated
239Pu and external gamma-rays (n=82) or to external gamma-rays only (n=18) and 50 unexposed
individuals served as controls. Peripheral blood was taken, RNA was isolated, converted into cDNA and
stored at -20°C. In previous analysis we screened the whole genome for radiation-associated candidate
genes and validated 15 mRNAs and 15 microRNAs using qRT-PCR. Within this analysis we examined the
association of these genes with 15 different chronic diseases. We examined the radiation-gene-disease
