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C-13-amino acid breath test as a tool for monitoring tumor growth
The Synthesis and Applications of Isotopically Labelled C o m p o u n d s
C-13-Amino Growth
Acid
B r e a t h T e s t as a Tool
for
Monitoring
Tumor
Maklko SUEHIRO, N a o m i OHSAWA*. Masato FUJIMAKI*, and Junji MORIKAWA**, Tokyo M e t r o p o l i t a n I n s t i t u t e of Gerontology. 35-2 Sakaecho. I t a b a s h l k u . T o k y o - 1 7 3 . * M i n s e i L i f e Science Institute, Koganelshi, **Elken Chemical Co.. Bunkyoku. Tokyo. Japan It I s w e l l known t h a t amino a c i d s a r e needed f o r tumor g r o w t h . We s t u d i e d i n r i v e amino a c i d o x i d a t i o n i n t o CO2 in tumor by means o f C-13-breath tests. I f o x i d a t i o n o f an amino a c i d in tumors can be d e t e c t e d as an i n c r e a s e in carbon-isotopically labeled CO2 in e x p i r e d b r e a t h f o l l o w i n g a d m i n i s t r a t i o n of tlle l a b e l e d amino a c i d . tumor g r o w t h might be d e t e c t a b l e i n r i v e . And If utilization o f t h e amino a c l d I s t u m o r - s p e c i f i c , growth of a s p e c i f i c tumor might be p r e d i c t a b l e . V a r i o u s tumors, i . e . y o l k sac. lung ( P C 8 , 1 0 ) . l i v e r ( I I 7 ) . and stomach ( 4 5 1 , 7 5 1 ) were t r a n s p l a n t e d s u b c u t a n e o u s l y i n t o t h e - - b a c k of 6-7 week-old athymic nude rats. 45-67 days after the t r a n s p l a n t a t i o n , C - 1 3 - b r e a t h t e s t s were performed u s i n g lOmg/kg of C - 1 3 - L - m e t h i o n i n e which was i n t r a v e n o u s l y a d m i n i s t e r e d Lo the r a t s . To t h e c o n t r o l r a t s w i t h o u t tumor and t h e r a t s beaLing DABi n d u c e d - h e p a t i c - t u m o r t h e b r e a t h t e s t s were a l s o performed. Among t h o s e t u m o r - b e a r i n g r a t s . t h e ones w i t h yolk s a c tumor showed markedly higher oxidation rate of methionine tllan the control rats. I n c r e a s e in w e i g h t o f t h e s e r a t s on t h e b a s i s of t h e w e i g h t on t h e t r a n s p l a n t a t i o n day was 85-96 ~. while that of control ones was 120-130 ~ and t h a t o f t i l e o t h e r tumor-bearing rats was 9 3 - 1 3 3 ~. A y o l k - s a c - t u m o r - b e a r i n g r a t which had no w e i g h t l o s s a f t e r 65 days o f t r a n s p l a n t a t i o n and t h e o t h e r t u m o r bearing rats showed no significant increase nor decrease in oxidation rate of methionine. No r e l a t i o n was observed between increase in the methionine utilization and alpha-fete protein production in tumor. Although for confirmative conclusion further investigation on various factors affecting the amino acid metabolism and tumor growth s h o u l d be c a r e f u l l y performed, t h e s e r e s u l t s might s u g g e s t that tumor growing in v a r i o u s o r g a n s or t i s s u e s needs specific amino acids, not any. and i f so b r e a t h t e s t s w i t h C-13 or C-14 amino acids could be used a s a s p e c i f i c tumor growth marker.
613
C-13-Amino Growth
Acid
B r e a t h T e s t as a Tool
for
Monitoring
Tumor
Maklko SUEHIRO, N a o m i OHSAWA*. Masato FUJIMAKI*, and Junji MORIKAWA**, Tokyo M e t r o p o l i t a n I n s t i t u t e of Gerontology. 35-2 Sakaecho. I t a b a s h l k u . T o k y o - 1 7 3 . * M i n s e i L i f e Science Institute, Koganelshi, **Elken Chemical Co.. Bunkyoku. Tokyo. Japan It I s w e l l known t h a t amino a c i d s a r e needed f o r tumor g r o w t h . We s t u d i e d i n r i v e amino a c i d o x i d a t i o n i n t o CO2 in tumor by means o f C-13-breath tests. I f o x i d a t i o n o f an amino a c i d in tumors can be d e t e c t e d as an i n c r e a s e in carbon-isotopically labeled CO2 in e x p i r e d b r e a t h f o l l o w i n g a d m i n i s t r a t i o n of tlle l a b e l e d amino a c i d . tumor g r o w t h might be d e t e c t a b l e i n r i v e . And If utilization o f t h e amino a c l d I s t u m o r - s p e c i f i c , growth of a s p e c i f i c tumor might be p r e d i c t a b l e . V a r i o u s tumors, i . e . y o l k sac. lung ( P C 8 , 1 0 ) . l i v e r ( I I 7 ) . and stomach ( 4 5 1 , 7 5 1 ) were t r a n s p l a n t e d s u b c u t a n e o u s l y i n t o t h e - - b a c k of 6-7 week-old athymic nude rats. 45-67 days after the t r a n s p l a n t a t i o n , C - 1 3 - b r e a t h t e s t s were performed u s i n g lOmg/kg of C - 1 3 - L - m e t h i o n i n e which was i n t r a v e n o u s l y a d m i n i s t e r e d Lo the r a t s . To t h e c o n t r o l r a t s w i t h o u t tumor and t h e r a t s beaLing DABi n d u c e d - h e p a t i c - t u m o r t h e b r e a t h t e s t s were a l s o performed. Among t h o s e t u m o r - b e a r i n g r a t s . t h e ones w i t h yolk s a c tumor showed markedly higher oxidation rate of methionine tllan the control rats. I n c r e a s e in w e i g h t o f t h e s e r a t s on t h e b a s i s of t h e w e i g h t on t h e t r a n s p l a n t a t i o n day was 85-96 ~. while that of control ones was 120-130 ~ and t h a t o f t i l e o t h e r tumor-bearing rats was 9 3 - 1 3 3 ~. A y o l k - s a c - t u m o r - b e a r i n g r a t which had no w e i g h t l o s s a f t e r 65 days o f t r a n s p l a n t a t i o n and t h e o t h e r t u m o r bearing rats showed no significant increase nor decrease in oxidation rate of methionine. No r e l a t i o n was observed between increase in the methionine utilization and alpha-fete protein production in tumor. Although for confirmative conclusion further investigation on various factors affecting the amino acid metabolism and tumor growth s h o u l d be c a r e f u l l y performed, t h e s e r e s u l t s might s u g g e s t that tumor growing in v a r i o u s o r g a n s or t i s s u e s needs specific amino acids, not any. and i f so b r e a t h t e s t s w i t h C-13 or C-14 amino acids could be used a s a s p e c i f i c tumor growth marker.
613