48th Meeting of the Particle Therapy Co-Operative Group
P a rticle T he ra p y C o -O p e ra tive Gro up (P T C O G ) 28.09. - 03.10.2009, He id e lb e rg
Heavy ions and X-rays in brain tumor treatment:
acomparison of their biological effects on tissue slice cultures
Meeting A bstract
P T C O G 48. Me e ting o f the P a rticle T he ra p y C o -O p e ra tive Gro up . He id e lb e rg ,
M. Müller - I ns titut für Klinis che Ne uro a na to m ie , Dr. Se nck e nb e rg is che Ana to m ie , Fra nk furt Ma in
F. Merz - I ns titut für Klinis che Ne uro a na to m ie , Dr. Se nck e nb e rg is che Ana to m ie , Fra nk furt Ma in
M. D urante - Ge s e lls cha ft für Schwe rio ne nfo rs chung , Da rm s ta d t
V. Seif ert - Klinik und P o lik linik für Ne uro chirurg ie , U nive rs itä ts k linik um Fra nk furt/
Ma in, Fra nk furt
J. Rieger - Dr. Se nck e nb e rg is che s I ns titut für Ne uro o nk o lo g ie , U nive rs itä ts k linik um Fra nk furt/ Ma in, Fra nk furt a m Ma in
M. Mittelbronn - Dr. Se nck e nb e rg is che s I ns titut für Ne uro o nk o lo g ie , U nive rs itä ts k linik um Fra nk furt/ Ma in, Fra nk furt a m Ma in
P . Harter - Dr. Se nck e nb e rg is che s I ns titut für Ne uro o nk o lo g ie , U nive rs itä ts k linik um Fra nk furt/ Ma in, Fra nk furt a m Ma in
I. Mishustin - FI AS Fra nk furt I ns titute fo r Ad va nce d Scie nce , Fra nk furt a m Ma in I. P shenichnov - FI AS Fra nk furt I ns titute fo r Ad va nce d Scie nce , Fra nk furt a m Ma in F. Rödel - Klinik für Stra hle nthe ra p ie und O nk o lo g ie , U nive rs itä ts k linik um Fra nk furt a m Ma in, Fra nk furt a m Ma in
H. Stöcker - FI AS Fra nk furt I ns titute fo r Ad va nce d Scie nce , Fra nk furt a m Ma in K. Schopow - Dr. Se nck e nb e rg is che Stiftung , Fra nk furt a m Ma in
F. D ehghani - I ns titut für Ex p e rim e nte lle Ne uro b io lo g ie , Dr. Se nck e nb e rg is che Ana to m ie , Fra nk furt a m Ma in
G. Taucher-Scholz - Ge s e lls cha ft für Schwe rio ne nfo rs chung , Da rm s ta d t I. Bechmann - I ns titut für Klinis che Ne uro a na to m ie , Dr. Se nck e nb e rg is che Ana to m ie , Fra nk furt Ma in
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28.09.-03.10.2009. Düs s e ld o rf: Ge rm a n Me d ica l Scie nce GMS P ub lis hing Ho us e ; 2009.
Do c09p tco g 142
DO I : 10.3205/09p tco g 142, U R N: urn:nb n:d e :0183-09p tco g 1420 Ve rö ffe ntlicht: 24. Se p te m b e r 2009
© 2009 Müller et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen
(http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de ). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.
Text
Background: I n this inte rd is cip lina ry p ro je ct, the b io lo g ica l e ffe cts o f he a vy io ns a re co m p a re d to tho s e o f X-ra ys us ing tis s ue s lice cu lture p re p a ra tio ns fro m ro d e nts a nd hum a ns . Ad va nta g e s o f this b io lo g ica l m o d e l a re the co ns e rva tio n o f a n o rg a no typ ic e nviro nm e nt a nd the ind e p e nd e ncy fro m g e ne tic im m o rta liz a tio n s tra te g ie s us e d to g e ne ra te ce ll line s . I ts o p e n a cce s s a llo ws e a s y tre a tm e nt a nd o b s e rva tio n via live -im a g ing m icro s co p y.
Materials and methods: R a t b ra ins a nd hum a n b ra in tum o r tis s ue a re cut into 300 µm thick tis s ue s lice s . T he s e s lice s a re cultiva te d us ing a m e m b ra ne -b a s e d cu lture
s ys te m a nd k e p t in a n incub a to r a t 37°C until tre a tm e nt. T he s lice s a re tre a te d with X-ra ys a t the ra d ia tio n fa cility o f the U nive rs ity Ho s p ita l in Fra nk furt a t d o s e s o f up to 40 Gy. T he he a vy io n irra d ia tio ns we re p e rfo rm e d a t the U NI LAC fa cility a t GSI with d iffe re nt io ns o f 11.4 A Me V a nd flue nce s ra ng ing fro m 0.5–10 x 106 p a rticle s /cm ².
U s ing 3D-co nfo ca l m icro s co p y, ce ll-d e a th a nd im m une ce ll a ctiva tio n o f the irra d ia te d s lice s a re a na lyz e d . P la nning o f the irra d ia tio n e x p e rim e nts is d o ne with s im ula tio n p ro g ra m s d e ve lo p e d a t GSI a nd FI AS.
Results: Afte r re ce iving a s ing le a p p lica tio n o f e ithe r X-ra ys o r he a vy io ns , s lice s we re k e p t in cu lture fo r up to 9d p o s t irra d ia tio n. DNA d a m a g e wa s vis ua liz e d us ing γ H2AX- s ta ining . He re , a d o s e -d e p e nd e nt incre a s e a nd tim e -d e p e nd e nt d e cre a s e co uld cle a rly b e o b s e rve d fo r the X-ra y irra d ia tio n. Slice s irra d ia te d with he a vy io ns s ho we d le s s γ H2AX-p o s itive ce lls d is trib ute d e ve nly thro ug ho ut the s lice , e ve n tho ug h p a rticle s we re ca lcu la te d to p e ne tra te o nly 90–100 µm into the s lice .
Conclusions: Sing le irra d ia tio ns o f b ra in tis s ue , e ve n a t hig h d o s e s o f 40 Gy, will re s ult ne ithe r in tis s ue d a m a g e vis ib le o n a m a cro s co p ic le ve l no r ne cro s is . T his is in line with the vie w tha t the b ra in is hig hly ra d io -re s is ta nt. Ho we ve r, DNA d a m a g e ca n b e d e te cte d ve ry we ll in tis s ue s lice s us ing γ H2AX-im m uno s ta ining . T hus , s lice culture s a re a n e x ce lle nt to o l to s tud y ra d ia tio n-ind uce d d a m a g e a nd re p a ir m e ch a nis m s in living tis s ue s .
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