Influence of Low Dose-Rate Radiation on Metabolism
Takashi SUGIHARA, Katsuyoshi FUJIKAWA, Satoshi TANAKA, Ignacia TANAKA,Jun-ichiro KOMURA
Department of Radiobiology
Abstract
To elucidate the influence of low dose-rate (LDR) radiation on metabolism, we have started
quantitative analysis of the amount of low molecular-weight metabolites (metabolome analysis) in the liverof B6C3F1 male and female mice irradiated at a LDR of 20 mGy/day for 300 days (total dose: 6,000 mGy).
Here we report preliminary results obtained this year. We observed changes in the amount of the compounds
involved in the TCA cycle, gluconeogenesis and glycolysis (for example, fumaric acid, malic acid,glyceraldehyde triphosphate and phosphoenolpyruvate) in both male and female irradiated mice. These
results suggest that metabolome analysis can be a useful tool for analyzing the biological effects of LDRradiation.

Non-irradiatedIrradiatedNon-irradiatedIrradiatedFig.1. Score plot of principal component analysis of the metabolites in the liver of male and female mice
irradiated or non-irradiated at 20 mGy/day for 300 days. n = 4.

0.15

Type2AsnHisPhe

Galactosamine
Glucosamine

Ascorbate 2-glucoside

Hexanoic acid
S-Methylglutathione
Xanthosine

Pro0.1

Type1Tyr

Gly

RiboflavinValdTDP-glucoseTaurocholic acid
UDP-N-acetylgalactosamine-1
UDP-N-acetylglucosamine-1

Isovaleric acidGDP-glucose
Ile Valericacid
GDP-mannose
GDP-galactose

PC2

XC0071

N-Acetylalanine

2-Hydroxyisobutyric acid
Ornithine
Hypotaurine
Cystathionine
Quinolinic acid
AMPUTP

Sarcosine

0XC0126
Trp
Heptanoic acid
1-Methyladenosine

UDP

Guanidinosuccinic acidOctanoic acid
Pyridoxamine 5'-phosphate

Daminozide
Ala-AlaType1

PenciclovirInosine
Octanoylcarnitine
Nicotinamide

Ser

Octanoyl CoA_divalent
Isovalerylcarnitine
Putrescine
N6-Acetyllysine Uric acid
Anthranilic acid
Taurine

Homocitrulline

PicolinicGDPacid
S-Lactoylglutathione

6-Phosphogluconic acid
Spermidine
Glucose 1-phosphate
Isethionicacid
Glucose 6-phosphate

UridineGulonolactone
Ribulose 5-phosphate
Dyphylline
Acetyl CoA_divalent
GlycerolN6-Methyl-2'-deoxyadenosine
Carnosine
Pyrophosphate
Thr-Asp
Metronidazole
3-Ureidopropionic acid
2-Phosphoglyceric
Acetoacetamide acid
β-Ala-LysGlutathioneGlycerophosphocholine(GSH)2-Methylserine
Aminoacetone
Uracil
1-Aminocyclopropane-1-carboxylic
XA0055Tyr-Arg_divalent
6-Hydroxyhexanoicacidp-Toluic acid
IMPacid-2Cys
Rhein
dIMP
2-Amino-3-phosphonopropionic
Homoserinelactone-2Arg
m-Toluic
acid
Hexylamine
Threonic acid acid
N1-Acetylspermidine
Butyrylcarnitine
Piperidine
2-Deoxyglucose 6-phosphate
Gly-Asp
3-Aminobutyricacid
N1-Methyl-4-pyridone-5-carboxamide
XC0016o-Toluic acid
Homocarnosine
XA0017
Glucaric acid
Cholic acid
Pantothenic acidCDP-cholineacid acid
Fructose 6-phosphate
Isobutyric acidSuccinic
Ascorbic
N-Acetylasparagine
Glutathione (GSSG)_divalentSedoheptulose 7-phosphate
Butyric acid
XC0089Homoserine
S-Adenosylhomocysteine
β-Ala
N-Acetylglucosamine 6-phosphate
Noradrenaline
N6,N6,N6-Trimethyllysine
XA0013
Propionyl CoA_divalent
N-Acetylhistidine
6-Hydroxydopamine
Ser-Glu
Isovalerylalanine-1
Cysteinesulfinic acid
4-Pyridoxicacid
Pipecolic acid Homovanillic UDP-N-acetylgalactosamine-2N-Acetylgalactosamine
acid
N-Acetylleucine-1
UDP-N-acetylglucosamine-2 N-Acetylmannosamine
Trimethylamine N-oxide
Hypoxanthine
1-Methylnicotinamide1-Methylhistidine
4-Acetamidobutanoic acid
Pelargonic acid
N-Acetylglucosamine
Thiamine
diphosphate
UDP-glucose
3-Methylhistidine
Triethanolamine
myo-Inositol
2-phosphate
CTP
Fructose 1,6-diphosphateMet
UDP-galactose
N-Acetylcysteine5,6,7,8-Tetrahydrobiopterin
threo-β-Methylasparticacid
XA0012
N-Acetyllysine
Gluconolactone
Gly-Gly
PRPP
FAD_divalent
Gly-Leu
N8-Acetylspermidine Dihydroxyacetone phosphate
Terephthalic acidcis-4-Hydroxyproline
Histamine
Spermine
Isovalerylalanine-2
CDP
DecanoicThymidine
acid
ADMA
N-Acetylleucine-2
XC0132
sulfoxide
Arg-Glu N-Acetylserine
DiethylaminomalonicMethionineacid
XA0035trans-Glutaconicacid
N-Glycolylneuraminicacid
1-Aminocyclopropane-1-carboxylic acid-1
N-Acetylaspartic acid
Glycocholic acidcis-Aconitic acid
Tyrosine
methyl ester
2'-Deoxycytidine
Isoglutamic acid
Homoserinelactone-1
ErgothioneineADP
Kynurenine Propionic acid
2-Hydroxyvalericacidacid
Imidazolelactic
acid
N-Acetylglutamic
AspGluNMN
Saccharopine
Lactic acid

0.05

AdenineTrimethylamine

Xanthine
Thr

N-Acetylglutamine

LysGlnIsobutyryl CoA_divalent

Cysteine glutathione disulfide
Glycerol 3-phosphate

Leu

Ala

N-AcetylglycineHydroxyproline

Thiamine GABA
Thiaproline

GTP

Phenaceturicacid
2-Hydroxybutyric acid
CMP-N-acetylneuraminate
Ascorbate 2-sulfate
S-Adenosylmethionine
UDP-glucuronic acid
Creatinine
O-Acetylhomoserine
γ-ButyrobetainecAMP
Octylamine
Adenosine
Octopamine
XA00193'-Dephospho
CoA
2-Aminoadipicacid
1-Methylhistamine
Glyceraldehyde 3-phosphate
ADP-ribose
PterinCysteic acid
N2-Acetylaminoadipic acid
Dopamine
Ethyl glucuronide5-Aminovaleric acid
XA0003
N-Acetylglucosamine 1-phosphate
5'-Deoxy-5'-methylthioadenosine
3-Indoxylsulfuricacid
Glutaric acid
Glucuronic acid-2ATP3-Aminoisobutyric acidNADH
N6-Methyllysine
3-Hydroxybutyric acidThiamine phosphate
N-Acetylneuraminicacid
Galacturonic acid-24-Amino-3-hydroxybutyricacid
5-Methyltetrahydrofolicacid
ribotide
2-Hydroxyglutaric acid
Ribose 5-phosphate5-Aminoimidazole-4-carboxamide
Ethanolamine
2,6-Diaminopimelic acid
N5-Ethylglutamine
AscorbateN-Acetylphenylalanine
2-phosphate
1H-Imidazole-4-propionic acidFMN
3-Phenylpropionic acidPyruvic acid
XA0065γ-Glu-2-aminobutyricacid
2-Hydroxy-4-methylvalericacid
XC0061
XA00273'-CMP
4-Guanidinobutyric
Diethanolamine acid
XC01372'-CMPN-Acetylmethionine
Theobromine5-Methoxyindoleacetic acid
Quinic acid
N-Acetylglucosylamine
3-Guanidinopropionic acid
7,8-Dihydrobiopterin
Isobutyrylcarnitine
Ribulose 1,5-diphosphate
5-Oxoproline
NADP+
NADPH_divalent
Adipicacid
Glucuronic acid-1
Guanidoacetic acid
1-Pyrroline 5-carboxylic acid
Mucic acid
S-Nitrosoglutathione
myo-Inositol 1-phosphate
Phosphoenolpyruvic acid
Galacturonic acid-1
BetaineImidazole-4-acetic acidN-Ethylmaleimide_+H2O
myo-Inositol 3-phosphate
2,3-Diphosphoglyceric acid
O-Acetylcarnitine
CMP
Phosphocreatine
Adenosine5'-phosphosulfate
Serotonin
SuccinylCoA_divalent
SDMA
CarboxymethyllysineMethylmalonyl CoA_divalent
Stachydrine
3',5'-ADP
Erythrose 4-phosphate
Malic acid
Betaine aldehyde_+H2O
Guanosine
Fumaric acid
CoA_divalent
XA00333-Phosphoglyceric acid
Ectoine3-Hydroxy-3-methylglutaric acid
UMP
Phosphorylcholine
Ophthalmic acid
Ethanolamine phosphatedCMP

N-Acetylornithineacid
Urea Gluconic
CholineN,N-Dimethylglycine
Citrulline
γ-Glu-Cys
O-SuccinylhomoserineNAD+
Anserine_divalent
Creatine
Argininosuccinic acid
Cytidine-0.05

N-Acetyl-β-alanine

GMP-0.1

1-Methyl-4-imidazoleaceticacid
Subericacid

Carnitine

2-Aminoisobutyric acid
Citric acid
2-Aminobutyric acid
Lauric acid
Myristoleic acid

Type2

Adenylosuccinic acid

-0.15
-0.15

-0.1

-0.05

00.05

0.1

0.15

PC1Fig.2.

Loading plot of principal component analysis.
We define substances with strong association only with principal component 1 as Type 1
and substances with strong association only with principal component 2 as Type 2.

♂Non-irradiated♂Irradiated♀Non-irradiated♀IrradiatedFig.3.

Relative amounts of metabolites illustrated on metabolic pathways (partial)