Radiation
Research Institute
Outline and Research Objectives
Radiation Research Institute (formerly called as Radioisotope Research Institute) wasestablished in 1992 for the purpose of radiation safety control of five radioisotope researchlaboratories belonging to Faculty of Medicine. They are located in basic science buildings,
Animal Center, University Hospital, and University Branch Hospital. (The laboratory in
University Branch Hospital was closed in March, 2002.) The research is also expected to theInstitute on the subjects related to radiations and radioisotopes such as radiation biology,
medical application of radiations/radioisotopes, and health physics.

Faculties and Students
Professor and Chair

Kunio Shinohara, Dr. of Medical
Science (1996-)
Lecturer
Takahiko Suzuki, Dr. of
Pharmaceutical Science
Research Student ....................1

Past Research and Major Accomplishments
I (K. Shinohara) learned applied physics at undergraduate course. After I got masters degree in biophysics, I took a doctoral course in medical science. In
the field of radiation biology, I started my research
work on the cytotoxic effects of γ-rays on cultured
mammalian cells in a colony state that is a model system for tumor cord [1]. Then the subject moved to
DNA damage and its repair induced by radiation andradiomimetic chemicals such as methylazoximethanol
acetate, an active principle of cycasin which is naturally occurring carcinogen in cycad, and benzo(a)pyrene.
When new radiation source, synchrotron radiation,
became available, our research subjects shifted tofocus on biological/medical application of monochromatic X-rays such as Auger enhancement of radiationinduced cell death and development and applicationof soft X-ray microscopy. In the mean time we foundthat to image hydrated specimens by soft X-ray
microscopy at high resolution, we need intense X-ray
source to image at a shorter time than the movement
by Brownian motion. For this purpose, we appliedlaser-produced plasma X-rays, by which the exposure
time was as short as 300 psec.
1. DNA damage and its repair induced by radiation and radiomimetic chemicals
With the aid of caffeine, we found that methylazoxymethanol acetate induces damage, which isrepaired by a mechanism analogous to post-replication repair of UV light-induced damage [3]. In this368

study, we used synchronized cells obtained by theautomatic synchronizer which we developed [2].
In the study of another carcinogen,benzo(a)pyrene, we detected the formation and excision repair of benzo(a)pyrine-DNA adducts in mammalian cells [4, 6]. This adducts were also detected inperipheral human lung tissue when the tissue wascultured in the presence of benzo(a)pyrene [5].
It is also observed that depression level of DNA
synthesis is well correlated to the sensitivity of cell
death to UV-irradiation in normal human cells and incells derived from xeroderma pigmentosum patient
deficient in DNA repair [8].
2. Radiation- and heat-induced cell death(1) Heat-induced cell death
Hyperthermia is developed as one of the method
for cancer treatment. The sensitivity of cell death
induced by the heat-treatment was studied withrespect to energy metabolism. It has been demonstrated that when the synthesis of ATP is inhibited,
sensitivity of the cell to heat increases [16]. Our
results show that ATP level decreases after heat-treatment and in a treatment-time dependent manner [15].
The sensitivity of cells to heat is well correlated to the
ATP level of the cells at normal growth condition
which corresponds to the pool size of ATP (or potential to synthesize ATP) [26,49]. The results indicatethat energy metabolism is a good marker to evaluate
heat sensitivity. We also observed that Ga citrate, atumor-seeking compound, is a good sensitizer to heat
treatment [17,47].
(2) Studies on radiation-induced cell death
X-rays inhibit DNA synthesis. Initiation of DNA
synthesis is much more sensitive to X-rays than its
elongation. We studied carefully this inhibition andresumption of replicon initiation after X-irradiation[7].
Synchrotron radiation is an intense radiation,

intense enough to study the effects of monochromatic
X-rays. We first studied an action spectrum of lethal
effects on mammalian cells in the wavelength range
from 160 to 254 nm. Cells were sensitive to 160 nm
and 254 nm and relatively resistant to 190 nm [9]. We
found that target site was not DNA but membrane at
the wavelength of 160 nm [13].
(3) Auger enhancement
When elements absorb X-rays at the inner shellelectrons, they release Auger electrons and are highly
toxic. Their LET corresponds to 5 MeV α particles(100 keV/µm). Therefore, efficient induction of Auger
effects in cells by X-rays will result in the sensitization to the cells. We studied this enhancement bylabeling the cells with 5-bromodeoxyuridine or 5iododeoxyuridine and monochromatic synchrotron
radiations at the wavelengths slightly higher than K
absorption edges of these elements (i.e., Br and I). Our
results are the first data for the Auger enhancementof cytotoxicity on mammalian cells obtained by synchrotron radiation [10,11]. Auger enhancement is also
observed in the induction of chromosome aberration[18]. Theoretical reports pointed the great enhancement and suggested the new possible modality forradiation therapy. However, our experimental results
were not in accord with this theory [11]. We re-evaluated this theoretical consideration and found that thetheory needs correction. Our correction of the theory
fits well to the experimental data [14]. This report[14] is cited in News and Views in Nature by John
Humm (336, 710-711, 1988). The results were against
the expectation for radiation therapy, but this is science. In the same issue of Nature, another method ofAuger enhancement was reported. The method basedon the nuclear resonance absorption of the element.
Although the results presented in the report could
have not been confirmed yet, the idea is attractive.
We estimated the enhancement ratio using the same
equation as above and found that more than 10 times
higher enhancement will be expectable [unpublishedresults]. However, it is hard to obtain the experimental data to evaluate this theoretical estimate at thepresent stage. To keep the potential to study Auger
enhancement, we tried to detect and characterize
Auger enhancement using laboratory X-ray source.
We observed small fraction of Auger enhancementthat was protectable by cysteamine as a proton donor
for radiation damage [41]. We also studied suicide
experiment with a radioisotope of iodine-125 [28].
(4) Molecular mechanisms of radiation-induced
cell death
Radiation-induced cell death has been classified
into two groups: reproductive death and interphase
death. Reproductive death is determined by thecolony forming ability, while interphase death isthought to be functional loss and estimated by loss ofmembrane function (as demonstrated by the dye
exclusion test) or energy metabolism. We first studied
the difference in these two modes of cell death. For
this purpose human leukemic MOLT-4 cells are well
suited. They show interphase death at relatively low
dose irradiation and also are able to be determined forthe colony forming ability. The data [29] show thatboth types of cell death occur in MOLT-4 cells andthat the mechanism of cell death is apoptosis. Next,
we compared MOLT-4 with M10, which is a radiosensitive mutant of L5178Y derived from mouse lymphocytic leukemia and has the same level of radiosensitivity. Unexpectedly, we found that M10 developed
necrosis, while MOLT-4 died by apoptosis at the same
dose level of irradiation [31]. It is confirmed with theheat-treatment that M10 has a system to induce apoptosis (, which is not working at X-irradiation,) probably by the different mechanism from MOLT-4 [31,42].
Based on these results, we are interested in themolecular mechanisms of radiation-induced apoptosis(MOLT-4) and necrosis (M10). Now we are focused on
the apoptosis in MOLT-4 cells. (Because of the lack of
manpower, radiation-induced necrosis in M10 isremained to be studied in future.) Radiation-induced
apoptosis in MOLT-4 cells is p53 dependent [45,48]
and caspase-3 dependent [50]. It should be noted that
inhibition of proteasome also induced apoptosis in
MOLT-4 cells probably with the different mechanism
from X-rays because both apoptosis were additive[39].

3. Development and application of soft X-ray
microscopy
Soft X-rays in a wavelength range of 1-10 nm areprovided by synchrotron radiation and moderately
absorbed by biological materials. Soft X-ray
microscopy has following advantages over optical andelectron microscopy: higher penetration depth thanelectron microscopy and higher resolution than optical microscopy. Therefore, with soft X-ray
microscopy, it is expected that we can observe awhole live cell at higher resolution than optical
microscopy. When we started this project, there wasno soft X-ray microscope. And now, internationally,
there are some microscopes with the potential toimage at a resolution of 20 nm. However, unfortunately, no active microscope at high resolution has beenworking in Japan. This is the present stage. Morethan 15 years ago, we were interested in soft X-ray
microscopy and started to study the importance of
this new method in biology.
When we started, the only method available forexperimental test was a contact microscopy using a369

thin film of polymethylmetacrylate (PMMA) that isdeveloped and characterized by IBM for industrial
purpose. We studied and applied it for imaging
human cells and chromosomes with some improvement of the method for the observation of PMMA bya transmission electron microscope [12]. We have succeeded in the observation of chromosome fibers andnucleosomes [19-21,33]. The results (Fig. 1) were top
data with respect to the resolution to image biologically meaningful specimen and were cited in books from
USA, China and Japan. Then we studied the condition
to image hydrated biological specimens including the
problem of radiation damage and image blurring byBrownian motion [22,24,25]. The conclusion of thisstudy proposed the use of short pulsed X-rays forimaging intact specimens in hydrated condition withsuccessful results for hydrated chromosomes with asingle shot exposure of laser-produced plasma X-rays
at the exposure time of 300 picoseconds [23,30,32].
However, our results were obtained by contact
microscopy and the method is good for molecules but
not well suited for imaging inside a whole cell.
Therefore, we proposed a possible microscope system
to image whole cells [27]. The system is now in thestage of development by other groups.
Another important factor for the application ofsoft X-ray microscopy to biological/medical science isthe contrast of the images for thick specimens. To
overcome this problem, specific staining with threedimensional observation may be the best choice. In
the case of soft X-rays, there is another possibility toidentify elements and molecules: spectroscopic analysis of imaging (spectromicroscopy). We have beenworking on spectromicroscopy in two aspects: instrumentation [43,44,46] and application [34,37]. This lineof work is in progress. For three-dimensional imaging,
we have also studied on holographic microscopy

Fig. 1. X-ray image of a stretched portion of a human chromosome [21]. An enlargement of the area indicated by an arrow in(a) is presented in (b).

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[35,36,38,40] and found that even with holographic
observation, three dimensional reconstruction may
not be possible with a single exposure.

Current Research
1. Radiation-induced cell death(1) Molecular mechanisms of radiation-induced
apoptosis
Our present study is focussed on the switchingmechanism of p53 to select DNA repair or to decidesuicide. For this study we are currently collecting thedata for p53, and related molecules and phenomenain each single cell to get the idea what is going on in
an individual single cell.
(2) Auger enhancement
As shown above, theoretical consideration showsthat Auger enhancement following nuclear resonanceabsorption is an attractive method. Although we havean idea to evaluate the theoretical results experimentally, we have no clue to apply this method for clinicaltumor therapy. Therefore, the work remains in theoretical level at the present stage.
(3) Cytotoxic effects of ultrahigh dose rate X-rays
Time scale of radiation effects on life begins withphysical interaction (10-18-10-15 sec) followed by chemical and biological processes. At a conventional
method of X-irradiation, these physical and chemical
processes will happen dispersively and induce ionization as one after another. In contrast, particle beamdensely ionizes irradiated materials and gives
increased cytotoxicity to cells. It is of interest to see
what will happen if one can concentrate ionization by
X-rays in a short instance especially in shorter than
one picosecond. Since such a radiation source is available in recent years, we started to study the cytotoxic
effects of ultrahigh dose rate X-rays on mammaliancells at the Institute of Laser Engineering, Osaka
University. Because of limited beam time, we are gradually correcting results and have no publication so far,though five years have already passed.

2. Development and application of soft X-ray
microscopy
Currently our subject is focussed on spectromicroscopy of the cell to understand images for the
improvement of contrast. We have collected images ofa cell at various wavelengths in a wide range (1-10nm). With absorption characteristics of elements andmolecules, we are trying to identify these elements
and molecules using computer-assisted image process-ing. The work is in collaboration with Prof. Ito of
School of Engineering, Tokai University.

Future Prospects
1. Radiation-induced cell death(1) Auger enhancement
It is not clear that Auger enhancement can beapplied for radiation therapy. However, I believe it isworth to continue studying.
(2) Ultrahigh dose rate X-rays in biology and medicine
The new radiation source may be a useful methodfor discovering the new mode of diagnostics and radiation therapy. At present the work is in the beginningstage. We will keep working on it.
(3) Molecular mechanisms of radiation-induced
apoptosis and necrosis
We are planning to understand the full scheme of
the flow of signal transduction process in an individual cell from DNA damage induced by X-rays to thedevelopment of apoptosis. The results will contributeto understand the whole scheme of apoptosis and to
explore the new mode of radiation therapy with theinduction of apoptosis.
2. Soft X-ray microscopy
We believe that soft X-ray microscopy will beestablished and applied to biological/medical research
as a complementary method to optical and electron
microscopy in future. The system will become compact and stay in laboratory in the size comparable to atransmission electron microscope.

Research Grants
1. Grant-in-Aid for Scientific Research (B) (1) [20012003] Studies on biological effects of ultrahigh dose
rate pulsed X-rays.
2. Grant-in-Aid for Scientific Research (A) (1) [19972000] Development and its medical/biological application of a projection X-ray microscope using synchrotron radiation.
3. Grant-in-Aid for Exploratory Research [1997-1998]
Studies on cytotoxic effects of ultrahigh dose rate Xrays.
4. Grant-in-Aid for Scientific Research (A) (1) [19951997] High resolution imaging analysis of elements
and molecules in a cell with an X-ray contact microscope.

Select Publications
1. Shinohara, K. and Okada, S.: Radiosensitivities ofmurine lymphoma L5178Y cells in a multi-cellularcolony system. J. Radiat. Res. 13, 109-116, 1972.
2. Okada, S. and Shinohara, K.: An automatic synchronizer for suspension culture of L5178Y cells. Cell
Tissue Kinet. 7, 195-199, 1974.
3. Shinohara, K. and Matsudaira H.: Evidence for caffeine-sensitive damage in methylazoxymethanol
acetate-treated L5178Y cells. Chem.-Biol. Interactions
12, 53-63, 1976.
4. Shinohara, K. and Cerutti, P.A.: Excision repair ofbenzo(a)pyrene-deoxyguanosine adducts in baby
hamster kidney 21/C13 cells and in secondary mouseembryo fibroblasts C57BL/6J. Proc. Nat’l. Acad. Sci.
USA 74, 979-983, 1977.
5. Shinohara, K. and Cerutti, P.A.: Formation of
benzo(a)pyrene-DNA adducts in peripheral humanlung tissue. Cancer Letters 3, 303-309, 1977.
6. Feldman, G., Remsen, J., Shinohara, K. and Cerutti,
P.A.: Excisability and persistence of benzo(a)pyrene
DNA adducts in epithelioid human lung cells. Nature
274, 796-798, 1978.
7. Shinohara, K. and Watanabe, I.: Inhibition andresumption of replicon initiation in X-irradiatedmouse L5178Y cells. Radiat. Environ. Biophys. 21,
163-173, 1983.
8. Shinohara, K.: Lethality and the depression of DNA
synthesis in UV-irradiated normal human and xeroderma pigmentosum cells. Mutation Res. 122, 385389, 1983.
9. Shinohara, K., Ito, T., Ito, A., Hieda, K., Kobayashi, K.
and Okada, S.: An approach to the use of synchrotron radiation for investigating radiation effects on
cultured mammalian cells in the range from 160 to
254 nm. Radiat. Res. 97, 211-215, 1984.
10. Shinohara, K., Ohara, H., Kobayashi, K., Maezawa,
H., Hieda, K., Okada, S. and Ito, T.: Enhanced killingof HeLa cells pre-labeled with 5-bromodeoxyuridine
by monochromatic synchrotron radiation at 0.9 Å:An evidence for Auger enhancement in mammaliancells. J. Radiat. Res. 26, 334-338, 1985.
11. Shinohara, K., Ohara, H., Hiraoka, T., Nakano, H.
and Ando, M.: Irradiation of cultured mammaliancells labeled with iododeoxyuridine by monochromatic synchrotron radiation at 0.370 and 0.380 Å.
Photon Factory Activity Report 1984/85, National
Laboratory for High Energy Physics, p. VI-153, 1986.
12. Shinohara, K., Aoki, S., Yanagihara, M., Yagishita, A.,
Iguchi, Y. and Tanaka, A.: A new approach to theobservation of the resist in X-ray contact
microscopy. Photochem. Photobiol. 44, 401-403,
1986.
13. Shinohara, K., Ito, A. and Ito, T.: Cell surface damage
in cultured mammalian cells with synchrotron radiation at 160 nm. Photochem. Photobiol. 44, 405-407,
1986.
14. Shinohara, K., Nakano, H., Hiraoka, T. and Ohara,
H.: Re-evaluation of the theoretical study of photon

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activation therapy. Photon Factory Activity Report
1986, National Laboratory for High Energy Physics,
p. 278, 1987.
15. Shinohara, K., Kugotani, M., Ishiwata, J. andMatsuda, T.: Early change of adenosine triphosphatelevels in L5178Y cells during hyperthermia. Jpn. J.
Cancer Res. (Gann) 78, 333-335, 1987.
16. Shinohara, K. and Matsuda, T.: Hyperthermia andcellular ATP levels. Radiosensitization Newsletter 6,
9-10, 1987.
17. Shinohara, K., Kawakami, N., Kugotani, M. andNakano, H.: Gallium citrate, a new sensitizer of cells
to hyperthermia. Jpn. J. Cancer Res. (Gann) 79, 2123, 1988.
18. Ohara, H., Shinohara, K., Kobayashi, K. and Ito, T.:
An additional enhancement in BrdU-labelled cultured mammalian cells with monoenergetic synchrotron radiation at 0.09 nm: Auger effect in mammalian cells. In “DNA Damage by Auger Emitters”(Ed. by K. F. Baverstock and D. E. Charlton), Taylor& Fancis, pp. 123-133, 1988.
19. Shinohara, K.: Observation of human chromosomeswith soft X-ray contact microscopy. SPIE 1140, 196200, 1989.
20. Shinohara, K.: Application of X-ray microscopy tomammalian cells. In “X-Ray Microscopy in Biology
and Medicine” (Ed. by Kunio Shinohara, Hiroshi
Kihara, Takuma Saito and Keiji Yada), Japan
Scientific Societies Press/Springer-Verlag, pp. 203212, 1990.
21. Shinohara, K., Nakano, H., Kinjo, Y. and Watanabe,M.: Fine structure of unstained human chromosome
fibres dried with no fixative as observed by X-ray
contact microscopy. J. Microscopy 158, 335-342,
1990.
22. Shinohara, K. and Ito, A.: Radiation damage in soft
X-ray microscopy of live mammalian cells. J.
Microscopy 161, 463-472, 1991.
23. Shinohara, K., Ito, A., Kinjo, Y. Watanabe, M.,
Kikuchi, Y. and Tanaka, K.A.: A simple chamber forhydrated specimen in a vacuum and its application
to X-ray contact microscopy with laser produced
plasma X-rays. In “X-RAY MICROSCOPY III” (Ed. by
A. Michette, G. Morrison and C. Buckley), Springer
Series in Optical Sciences Vol. 67, Springer-Verlag,
pp. 347-349, 1992.
24. Shinohara, K. and Ito, A.: Factors affecting the observation of hydrated mammalian cells by soft X-ray
microscopy. In “X-RAY MICROSCOPY III” (Ed. by A.
Michette, G. Morrison and C. Buckley), Springer
Series in Optical Sciences Vol. 67, Springer-Verlag,
pp. 397-399, 1992.
25. Ito, A. and Shinohara, K.: Image blurring by thermal
diffusion in the observation of hydrated biomolecules with soft X-ray microscopy. Cell Structure andFunction 17, 209-212, 1992.
26. Shinohara, K., Kawakami, N., Ito, A., Kugotani, M.,
Nakano, H., Ishiwata, J. and Matsuda, T.: The role of
ATP metabolism in hyperthermic cell killing. In“Cancer Treatment by Hyperthermia, Radiation and372

Drugs” (Ed. by T. Matsuda), Taylor and Francis, pp.
79-91, 1993.
27. Richardson, M., Shinohara, K., Kinjo, Y., Tanaka,
K.A., Ikeda, H. and Kado, M.: Pulsed X-ray
microscopy of biological specimens with laser plasma
source. SPIE 1741, 133-141, 1993.
28. Miyazaki, N. and Shinohara, K.: Cell killing induced
by decay of 125I during the cell cycle: comparison of
125
I-antipyrine with 125I-bovine serum albumin. Radiat.
Res. 133, 182-186, 1993.
29. Shinohara, K. and Nakano, H.: Interphase death andreproductive death in X-irradiated MOLT-4 cells.
Radiat. Res. 135, 197-205, 1993.
30. Shinohara, K., Ito, A. and Kinjo, Y.: X-ray microscopyof biological specimens with laser plasma X-rays.
SPIE 2015, 10-19, 1994.
31. Nakano, H. and Shinohara, K.: X-ray-induced cell
death: apoptosis and necrosis. Radiat. Res. 140, 1-9,
1994.
32. Kinjo, Y., Shinohara, K., Ito, A., Nakano, H.,
Watanabe, M., Horiike, Y., Kikuchi, Y., Richardson,
M.C. and Tanaka, K.A.: Direct imaging in a waterlayer of human chromosome fibres composed of
nucleosomes and their higher-order structures bylaser plasma X-ray contact microscopy. J. Microscopy
176, 63-74, 1994.
33. Shinohara, K., Yada, K. and Kinjo, Y.: X-ray
microscopy of chromosome structures. In “X-ray
Microscopy IV” (Ed. by A. I. Erko and V. V. Aristov),
Bogorodskii Pechatnik Publishing Company, pp. 213216, 1994.
34. Shinohara, K., Ito, A., Matsumura, T., Kinoshita, K.
and Kobayashi, K.: Absorption spectra at the wavelength range of 1.5-10 nm and element-imaging of
cultured mammalian cells with electronic zooming
tube. In “X-ray Microscopy IV” (Ed. by A. I. Erko and
V. V. Aristov), Bogorodskii Pechatnik Publishing
Company, pp. 264-267, 1994.
35. Daido, H., Schulz, M.S., Murai, K., Kodama, R., Yuan,
G., Goto, J., Tanaka, K.A., Kato, Y., Nakai, S.,
Shinohara, K., Honda, T., Kodama, I., Iwasaki, H.,
Yshinobu, T., Tsukamoto, M., Niibe, M., Fukuda, Y.,
Neely, D., MacPhee, A. and Slark, G.: Subnano-second in-line soft X-ray holography using germanium
laser in the 20 nm wavelength region. J. X-ray Sci.
Technol. 5, 105-120, 1995.
36. Shinohara, K., Ito, A., Nakano, H., Kodama, I.,
Honda, T., Matsumura, T. and Kinoshita, K.: X-ray
holographic microscopy of biological specimens with
an electronic zooming tube. J. Synchrotron Radiat. 3,
35-40, 1996.
37. Ito, A., Shinohara, K., Nakano, H., Matsumura, T.
and Kinoshita, K.: Measurement of soft X-ray absorption spectra and elemental analysis in local regionsof mammalian cells using an electronic zooming
tube. J. Microscopy 181, 54-60, 1996.
38. Kodama, I., Yamaguchi, M., Ohyama, N., Honda, T.,
Shinohara, K., Ito, A., T., Matsumura, T., Kinoshita,
K. and Yada, K.: Image reconstruction from an in-line

X-ray hologram with intensity distribution constraint. Optics Commun. 125, 36-42, 1996.
39. Shinohara, K., Tomioka, M., Nakano, H., Toné, S.,
Ito, H. and Kawashima, S.: Apoptosis induction
resulting from proteasome inhibition. Biochem. J.
317, 385-388, 1996.
40. Shinohara, K.: Possible applications of X-ray lasers inbiology: X-ray microscopy and X-ray lasers. In “X-ray
Lasers 1996” (Ed. by S. Svanberg and C.-G.
Wahlstrom), Institute of Physics Conference Series
Number 151, Institute of Physics, pp. 533-538, 1996.
41. Shinohara, K., Nakano, H. and Ohara, H.: Detectionof Auger enhancement induced in HeLa cells labeledwith iododeoxyuridine and irradiated with 150 kV
X-rays: Effects of cysteamine and dimethylsulfoxide.
Acta Oncologica 35, 869-875, 1996.
42. Nakano, H., Kurihara, K., Okamoto, M., Toné, S. andShinohara, K.: Heat-induced apoptosis and p53 in
cultured mammalian cells. Int. J. Radiat. Biol. 71,
519-529, 1997.
43. Ito, A., Shinohara, K., Mizukami, Y., Nakano, H.,
Yada, K., Uehara, T. and Honda, T.: X-ray contact
microscopy system for spectromicroscopy of biological specimens. J. Synchrotron Radiat. 5, 1099-1101,
1998.
44. Shinohara, K., Ito, A., Nakano, H., Honda, T. and
Yada, K.: X-ray microscopy system with an electronic
zooming tube. In “X-Ray Microscopy andSpectromicroscopy” (Ed. by J. Thieme, G. Schmahl, E.
Umbach and D. Rudolph), Springer-Verlag, pp. I-169I-173, 1998.
45. Nakano, H. and Shinohara, K.: Correlation between
unirradiated cell TP53 protein levels and radiosensitivity in MOLT-4 cells. Radiat. Res. 151, 686-693,
1999.
46. Shinohara, K., Ito, A., Honda, T., Yoshimura, H. and
Yada, K.: Development of an X-ray projection microscope using synchrotron radiation. In “X-Ray
Microscopy: Proceedings of the Sixth International
Conference” (Ed. by W. Meyer-Ilse, T. Warwick, and
D. Attwood), AIP Conference Proceedings 507,
American Institute of Physics, pp. 346-349, 2000.
47. Miyazaki, N., Nakano, H., Kawakami, N., Kugotani,M., Nishihara, K., Aoki, Y. and Shinohara, K.:
Sensitizing effects of gallium citrate on hyperthermic
cell killing in vitro. Int. J. Hyperthermia 16, 457-470,
2000.
48. Nakano, H., Kohara, M. and Shinohara, K.:
Evaluation of the relative contribution of a p53-mediated pathway in X-ray-induced apoptosis in MOLT-4
cells by transfection with mutant p53 gene at different expression levels. Cell Tissue Res. 306, 101-106,
2001.
49. Miyazaki, N., Kurihara, K., Nakano, H. andShinohara, K.: Role of ATP in the sensitivity to heatand the induction of apoptosis in mammalian cells.
Int. J. Hyperthermia 18, 316-331, 2002.
50. Nakano, H. and Shinohara, K.: Time sequence analysis of caspase-3-independent programmed cell death

and apoptosis in X-irradiated human leukemic
MOLT-4 cells. Cell Tissue Res., 310, 305-311, 2002.

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