CN109825568A - Radiosensitive gene marker and the application in the low LET ray radiation of identification - Google Patents
Radiosensitive gene marker and the application in the low LET ray radiation of identification Download PDFInfo
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Abstract
The present invention provides radiosensitive gene marker and identifying the application in low LET ray radiation.The radiosensitive gene marker includes Wnt7b, Tprkb, Pira1, Pde4dip, Limk2, Ctns, Kcnk6, Csf2rb, Cd80 and Sesn2.The gene expression dose of radiosensitive gene marker in the organism radiated based on detection, for whether identifying the organism radiated by low LET ray (such as: X-ray, β ray, gamma-rays) radioactive exposure, to provide dose of radiation reference, it to be used for nuclear radiation injury risk assessment.
Description
Technical field
The invention belongs to radiobiology ray type detection fields, and in particular to radiosensitive gene marker and reflect
Application in not low LET ray radiation.
Background technique
X-ray and other low linear energy transfer (Linear energy transfer, LET) ray such as β, gamma-rays, electricity
Sub-line etc. has in each fields such as health care, industrial and agricultural production, extraordinary medicine, scientific researches is widely applied basis.LET is to comment
One parameter of valence ray matter.Relative to high LET ray (such as heavy ion, fast neutron, carbon, nitrogen, oxygen, neon), low LET ray exists
The density of ionization is obviously less than normal in unit length, the scattering process highly significant of ray.In addition being worn as what electromagnetic wave itself had
The radiation protection of penetration effect, fluorescent effect etc., x-ray also becomes the problem of increasingly paying close attention to.
In daily a large amount of use CT examinations and tumour radiotherapy, it is based especially on digital radiography or Digital Subtraction
The orthopaedics of angiography, carcinoma intervention, in cardiac conduction bundle branch ablative surgery, the radioactive protection tool of medical staff includes lead
Clothing, muffler, eyeshade etc. can not often obstruct x-ray in art completely.Lead to related and adjacent department's (as above lower floor operating room) doctor
There is the morbidity of the malignant tumours such as significantly raised thyroid cancer, breast cancer in shield personnel.In addition to the application of X-ray medically,
Low LET ray has been widely used in that industrial exploration, weapon be armoring and the fields such as metal quality detection, anti-terrorism safety check at present.It is short
Phase high dose or the low LET ray accumulation of long-term low dose have become the health effect of practitioner and check object wide at present
The problem of general concern.Low LET line can cause irreversible damage to body, it is possible to cause malignant tumour, disease in the blood system
And the adverse reactions such as inflammation fibrosis.
In addition, low LET ray is also one of the ray type released in nuclear weapon explosion (such as β particle, gamma-rays).
The electromagnetic wave weapon protection faced in modern war is similarly related to various low LET rays.Potential radiation threat may also originate from
Industrial flaw detection use or medical radiation course are destroyed or radiate once radioactive source leakproofness occurs in transhipment, storage, operational process
Source is lost, and low LET ray radiation can be caused.Radiation hygiene and health monitoring towards practitioner successfully manage various types of radiation
Emergency event effectively distinguish to exposed ray and determines increasingly to be taken seriously based on biological effect.This will be to core
Safety, the processing of radiation accident, the timely appropriate treatment of exposed population group all have critical significance.
Summary of the invention
Based on problem of the existing technology, the first object of the present invention is to provide radiosensitive gene marker, should
The radiosensitive gene marker defending party to the application confirms only in low linear energy transfer (low-linear energy
Transfer, LET) radiosusceptibility of the ray (such as X-ray) with high special, to High Linear energy transmission (high-
Linear energy transfer, LET) ray (such as Heavy ion beam) radiationless sensibility.
The second object of the present invention is that providing the radiosensitive gene marker is identifying answering in low LET ray radiation
With.The gene expression dose of radiosensitive gene marker in the organism radiated based on detection, for identifying by spoke
Whether the organism penetrated is by low LET ray (such as: X-ray, β ray, gamma-rays) radioactive exposure, to provide dose of radiation ginseng
It examines.
The third object of the present invention is to provide a kind of for whether identifying organism by the kit of low LET ray radiation
And its application, it being capable of quicker, convenient and accurate mirror using the kit containing the radiosensitive gene marker of the present invention
Not low LET ray simultaneously provides dosage reference.
The fourth object of the present invention is to provide a kind of method for obtaining the radiosensitive gene marker of the present invention.
The purpose of the present invention is achieved by following technological means:
In a first aspect, radiosensitive gene marker provided by the invention, which includes 10
Radiosensitive gene: Wnt7b (Wnt Family Member 7B, Wnt family protein 7 b), Tprkb (TP53-Related
Protein Kinase Binding Protein, TP53 related protein kinase binding protein), Pira1 (Paired-Ig-Like
Receptor A1, with p- Ig- sample receptor A1), Pde4dip (Phosphodiesterase 4D Interacting
Protein, phosphodiesterase 4 D interaction protein), Limk2 (LIM Domain Kinase 2, the domain LIM kinases 2), Ctns
(Cystinosin, Lysosomal Cystine Transporter, cystine, lysosome cystine transport protein), Kcnk6
(Potassium Two Pore Domain Channel Subfamily K Member 6, potassium diplopore domain channel subfamily K at
Member is 6), (Colony Stimulating Factor 2Receptor Beta Common Subunit, bacterium colony stimulate Csf2rb
2 receptor β common subunit of the factor), Cd80 (Cd80Molecular, Cd80 molecule) and Sesn2 (2 egg of Sestrin 2, Sestrin
It is white).
In above-mentioned radiosensitive gene marker, it is preferable that the nucleotide sequence of the Wnt7b is as follows:
AGAGAGGTGGTTAGTGGACCCAGGCAGGGCACTGGCTGTCCCAATGCTGT (as shown in SEQ ID NO:1)
(5'-3')；
The nucleotide sequence of the Tprkb is as follows:
GCGCCAAGTCTGCAAAGCCAGGTGCTCTCATAGTGCAGTTCTGGGGTTGT (as shown in SEQ ID NO:2)
(5'-3')；
The nucleotide sequence of the Pira1 is as follows:
CCAGGATCTGTGATCGCCTCCAAAAGAGCAATGACCATCTGGTGTCAGGG (as shown in SEQ ID NO:3)
(5'-3')；
The nucleotide sequence of the Pde4dip is as follows:
GGGGGGAAGGAACTAATGACATCGTCTCAGACGTTCATCTCTAACCAGCC (as shown in SEQ ID NO:4)
(5'-3')；
The nucleotide sequence of the Limk2 is as follows:
TGAGTATGCTTGCACTGTCCCCAGCAAGTGTGGGAGTGGGGCCTGCACTA (as shown in SEQ ID NO:5)
(5'-3')；
The nucleotide sequence of the Ctns is as follows:
GCCTTCAGAACCAAGTCCTGGGGGCTTAGAGGACCTTGCTTACCTATGTC (as shown in SEQ ID NO:6)
(5'-3')；
The nucleotide sequence of the Kcnk6 is as follows:
CAGAGCCCAAGCCACATCTACTACTGTGTGCCTAGCACAGAAAAGCATGG (as shown in SEQ ID NO:7)
(5'-3')；
The nucleotide sequence of the Csf2rb is as follows:
TGAGCACACATTCCAGGTCCAGTACAAGAAGAAATCGGACAGCTGGGAGG (as shown in SEQ ID NO:8)
(5'-3')；
The nucleotide sequence of the Cd80 is as follows:
GCTCTTTGGGGCAGGATTCGGCGCAGTAATAACAGTCGTCGTCATCGTTG (as shown in SEQ ID NO:9)
(5'-3')；
The nucleotide sequence of the Sesn2 is as follows:
TGGCTGCCTGTGTGGGAGAGGAGTAAGGACCTCCAGGGACTAGCACTCCA is (such as SEQ ID NO:10 institute
Show) (5 ' -3 ').
Second aspect, the present invention also provides above-mentioned radiosensitive gene markers to identify answering in low LET ray radiation
With.
In above-mentioned application, it is preferable that the application the following steps are included:
Detect radiosensitive gene marker Wnt7b, Tprkb in the organism that is radiated, Pira1, Pde4dip,
The gene expression dose of Limk2, Ctns, Kcnk6, Csf2rb, Cd80 and Sesn2, when its expression occur it is significant to a high-profile,
It can then identify and determine that the organism radiated is the exposure of low LET ray radiation.
In above-mentioned application, the organism may include people, animal etc..
In above-mentioned application, it is preferable that the low LET ray include one of X-ray, β ray and gamma-rays etc. or
It is a variety of.
In above-mentioned application, it is preferable that the gene expression dose of the sensitive gene marker is its transcriptional level difference
Express the average value of multiple.
The third aspect, the present invention also provides a kind of for whether identifying organism by the kit of low LET ray radiation, institute
It states kit and contains above-mentioned radiosensitive gene marker.
Fourth aspect, the present invention also provides above-mentioned kits to identify the application in low LET ray radiation.
5th aspect, the present invention also provides a kind of sides that above-mentioned radiosensitive gene marker is obtained with non-treatment purpose
Method includes the following steps:
After carrying out different ray types, the irradiation of various dose single graded doses and the irradiation of gradation graded doses to mouse,
It extracts fresh lung tissue and does genetic chip or real-time quantitative polymerase chain reaction, based on full-length genome gene expression arrays to 24
All lung tissue full-length genome expressions are analyzed, and different radiation exposures, the trend pass of dose of radiation and gene expression are analyzed
System, obtain gene expression amount increase and increase with low LET ray radiation dosage, and not with high LET ray radiation doses change and
The expressing gene of variation combines, i.e. the radiosensitive gene marker.
In above-mentioned method, different ray types, the irradiation of various dose single graded doses and the irradiation of gradation graded doses
It can take such as under type, such as: x-ray graded doses single fraction irradiation (0,10.5,12.5,14.5,17.5Gy), x-ray gradient agent
Measure fractionation of radiation (0,10,20, points of 5 times 30,40Gy irradiations), carbon ion (Carbon-ions) graded doses single fraction irradiation (0,
7.5,10.5,12.5,14.5Gy), carbon ion (Carbon-ions) graded doses fractionation of radiation (0,5,10,15,20Gy points 5 times
Irradiation).
In above-mentioned method, it is preferable that the difference ray type includes low LET ray and high LET ray；More preferably
Ground, the high LET ray include one of fast neutron ray, negative πmeson ray and Heavy ion beam etc. or a variety of.
The present invention is by being turned after x-ray or other low LET radiation exposures according to mouse lung tissue coherent radiation sensitive gene
Record level stress sexually revise and a kind of biological dosage evaluation measures for establishing.
The present invention receives full-length genome transcription group Analysis and Screening in 24 weeks after the different full lung irradiations of LET ray using mouse
The relevant sensitization assortment of genes out.Specific gene combination is reactionless to high LET ray, but receives energy after low LET radiation exposure
It enough drives the assortment of genes significant lofty tone occur, and by the biological effect, mould is predicted according to gene expression dose-X-ray
Type quickly carries out X-ray radiation identification.
The mouse model that the present invention takes is mouse induced lung injury model, is research radiation pneumonitis, lung fiber
Change and dose of radiation relationship, normal tissue radioreaction, respiratory disease and immune response mechanism important tool,
There is irreplaceable role in radioecology, radiotherapeutics and anti-injury of lungs medicament research and development.Induced lung injury early stage
It is mainly shown as radiation pneumonitis (usually secondary in 3 months after irradiation), exempts from since a large amount of T lymphocytes are generated by activation
Epidemic disease responsing reaction, a kind of lymphatic pulmonary alveolitis；Advanced stage can develop as interstitial pulmonary fibrosis (after irradiation 6 months or so).
The pathophysiological processes of mouse induced lung injury and the mankind are very much like, therefore can be used as reliable reference experiment mould
Type.
In the present invention, if organism is received to be hybrid ray, i.e., contain the feelings of high LET ray, low LET ray simultaneously
Shape, the method for the present invention can accurately identify low LET ray portion.
Beneficial effects of the present invention:
(1) radiosensitive gene marker of the invention is only in low linear energy transfer (low-linear energy
Transfer, LET) radiosusceptibility of the ray (such as X-ray) with high special, to High Linear energy transmission (high-
Linear energy transfer, LET) ray (such as Heavy ion beam) radiationless sensibility, it is radiated based on detection
Whether the gene expression dose of radiosensitive gene marker in organism is low for identifying the organism radiated
LET ray (such as: X-ray, β ray, gamma-rays) radioactive exposure is used for nuclear radiation injury to provide dose of radiation reference
Risk assessment.
It (2) can be quicker, convenient and accurate using the kit containing the radiosensitive gene marker of the present invention
Identify low LET ray and dosage reference is provided.
Detailed description of the invention
Fig. 1 is that C57BL/6 mouse receives different ray types, various dose single graded doses in the embodiment of the present invention 1
After irradiation and the irradiation of gradation graded doses, dose-dependent up-regulation base is obtained after lung tissue full-length genome transcriptional level analysis in 24 weeks
Because (dose-dependent up-regulation genes) subset Vean diagram [x-ray graded doses single fraction irradiation (0,10.5,
12.5,14.5,17.5Gy), x-ray graded doses fractionation of radiation (0,10,20, points of 5 times 30,40Gy irradiations), carbon ion
(Carbon-ions) graded doses single fraction irradiation (0,7.5,10.5,12.5,14.5Gy), carbon ion (Carbon-ions) gradient
Dosage fractionation irradiation (0,5,10,15,20Gy points of 5 irradiations)].
Fig. 2 is 126 X-ray specific gene thermal maps that Wien map analysis obtains in the embodiment of the present invention 1.
Fig. 3 is the low of most significant (Top 10) the X-ray specific gene composition of Wien map analysis in the embodiment of the present invention 1
The gene thermal map of the LET ray biological differentiation assortment of genes.
Fig. 4 is 10 of acquisition specific sensitive genes are sieved in the embodiment of the present invention 2 after x-ray bombardment expression in 24 weeks
It measures (log2fold-change).
Fig. 5 is that 10 specific sensitive genes of acquisition are sieved in the embodiment of the present invention 2 in graded doses X-ray, heavy ion
24 weeks gene expression values (P < 0.0001) after irradiation.
Fig. 6 is 10 in the embodiment of the present invention 2 specific sensitive genes 24 after graded doses X-ray, heavy ions
The gene expression values in week.
Specific embodiment
In order to which technical characteristic of the invention, purpose and beneficial effect are more clearly understood, now to skill of the invention
Art scheme carries out described further below, but should not be understood as that limiting the scope of the invention.
Chemical reagent employed in following embodiment etc., if being commercially available acquisition without specified otherwise.
The screening of the radiosensitive gene marker of embodiment 1 obtains
1, zoopery irradiation and grouping: using 8-10 week old C57BL6 female mice, and SPF grade are raised, and rearing conditions are,
Temperature (23 ± 1) DEG C, relative humidity 55% ± 5%, pressure difference≤10Pa, daily illumination 12h, drinking-water of freely ingesting.
2, it is transferred to dedicated mouse chest irradiation device after isoflurane induced anesthesia before irradiation and properly fixes.Using X
Line and heavy ion (carbon ion, carbon-ions) ray carry out full lung field irradiation.X-ray is one of the representative of low LET ray, is
(energy 6-10MV) is irradiated after clinac accelerates.As the main representative of high LET ray, Heavy ion beam be through
The carbon particle line (energy 280MeV) that cyclotron (diameter reach 20-30 meter) drains after accelerating, with high energy and
Speed.
3, irradiating and being grouped includes x-ray graded doses single fraction irradiation: 0,10.5,12.5,14.5,17.5Gy, x-ray gradient agent
Measure fractionation of radiation: 0,10,20,30,40Gy points of 5 irradiations, heavy ion graded doses single fraction irradiations: 0,7.5,10.5,12.5,
14.5Gy, heavy ion graded doses fractionation of radiation: 0,5,10,15,20Gy points of 5 irradiations.
4, blank control group does not receive radiation exposure (0Gy).Control group and every group of each dosage experiments group are randomly assigned 3
Mouse.
5, the 24th week row takes fresh lung tissue, uses RNeasy after total serum IgE extraction agent (Trizol) processing after irradiating
Mini kit separation and Extraction total serum IgE.In order to avoid DNA pollution, RNA is handled with DNase I.The RNA of purifying 45.0 μ l without
It is eluted in the water of nuclease, and -20.0 DEG C of storages.RNA concentration and pure is assessed using NanoDrop ND-1000 spectrophotometer
Degree.Use the integrality and purity of 2100Bioanalyzer and corresponding RNA Nano Chip measurement RNA sample.Based on full base
Because group gene expression arrays analyze sample.The generation of expression matrix, data notes and place are carried out using included software package
Reason.In subsequent statistical test, log2 conversion is carried out to data to illustrate that the expression of gene rises or declines.To analyze not
With time point radiation and gene expression trend relationship, clustering, including principal component analysis, layer are carried out using R lingware packet
Secondary cluster, K mean cluster and Self-organizing Maps identify dosage related gene expression.
24 weeks lung tissue full-length genome expressions are analyzed based on full-length genome gene expression arrays, analysis is different
The trend relationship of radiation exposure, dose of radiation and gene expression, obtain gene expression amount increase with low LET ray radiation dosage and
The expressing gene combination for increasing, and not changing with high LET ray radiation doses change, the i.e. radiosensitive gene marker.
Specific screening process is as follows:
Referring to Fig. 1 and Fig. 2, x-ray graded doses single fraction irradiation (0,10.5,12.5,14.5,17.5Gy), x-ray graded doses
Fractionation of radiation (0,10,20, points of 5 times 30,40Gy irradiations), carbon ion (Carbon-ions) graded doses single fraction irradiation (0,7.5,
10.5,12.5,14.5Gy), carbon ion (Carbon-ions) graded doses fractionation of radiation (0,5,10,15,20Gy point 5 photographs
Penetrate) 24 weeks afterwards, dose-dependent up-regulation gene (dose-dependent is obtained after the analysis of lung tissue full-length genome transcriptional level
Up-regulation genes) subset.Wien map analysis obtains 126 X-ray specific genes.
Referring to Fig. 3, respectively to after different radiation exposures mouse lung tissue gene expression dose carry out thermal map analysis shows that: base
It is increased because expression quantity increases with x-ray dose, is in dosage correlation；Gene expression amount not with Heavy ion beam doses change and
Change.Screening obtains 10 radiosensitive assortments of genes: Wnt7b (Wnt Family Member 7B, Wnt family protein
7b), Tprkb (TP53-Related Protein Kinase Binding Protein, TP53 related protein kinase combination egg
It is white), Pira1 (Paired-Ig-Like Receptor A1, match p- Ig- sample receptor A1), Pde4dip
(Phosphodiesterase 4D Interacting Protein, phosphodiesterase 4 D interaction protein), Limk2 (LIM
The domain Domain Kinase 2, LIM kinases 2), Ctns (Cystinosin, Lysosomal Cystine Transporter, Guang
Propylhomoserin, lysosome cystine transport protein), Kcnk6 (Potassium Two Pore Domain Channel Subfamily
K Member 6, potassium diplopore domain channel subfamily K member 6), Csf2rb (Colony Stimulating Factor
2Receptor Beta Common Subunit, 2 receptor β common subunit of colony stimulating factor), Cd80 (Cd80Molecular,
Cd80 molecule) and Sesn2 (2 albumen of Sestrin 2, Sestrin).
In above-mentioned radiosensitive gene marker, it is preferable that the nucleotide sequence of the Wnt7b is as follows:
AGAGAGGTGGTTAGTGGACCCAGGCAGGGCACTGGCTGTCCCAATGCTGT (as shown in SEQ ID NO:1)
(5'-3')；
The nucleotide sequence of the Tprkb is as follows:
GCGCCAAGTCTGCAAAGCCAGGTGCTCTCATAGTGCAGTTCTGGGGTTGT (as shown in SEQ ID NO:2)
(5'-3')；
The nucleotide sequence of the Pira1 is as follows:
CCAGGATCTGTGATCGCCTCCAAAAGAGCAATGACCATCTGGTGTCAGGG (as shown in SEQ ID NO:3)
(5'-3')；
The nucleotide sequence of the Pde4dip is as follows:
GGGGGGAAGGAACTAATGACATCGTCTCAGACGTTCATCTCTAACCAGCC (as shown in SEQ ID NO:4)
(5'-3')；
The nucleotide sequence of the Limk2 is as follows:
TGAGTATGCTTGCACTGTCCCCAGCAAGTGTGGGAGTGGGGCCTGCACTA (as shown in SEQ ID NO:5)
(5'-3')；
The nucleotide sequence of the Ctns is as follows:
GCCTTCAGAACCAAGTCCTGGGGGCTTAGAGGACCTTGCTTACCTATGTC (as shown in SEQ ID NO:6)
(5'-3')；
The nucleotide sequence of the Kcnk6 is as follows:
CAGAGCCCAAGCCACATCTACTACTGTGTGCCTAGCACAGAAAAGCATGG (as shown in SEQ ID NO:7)
(5'-3')；
The nucleotide sequence of the Csf2rb is as follows:
TGAGCACACATTCCAGGTCCAGTACAAGAAGAAATCGGACAGCTGGGAGG (as shown in SEQ ID NO:8)
(5'-3')；
The nucleotide sequence of the Cd80 is as follows:
GCTCTTTGGGGCAGGATTCGGCGCAGTAATAACAGTCGTCGTCATCGTTG (as shown in SEQ ID NO:9)
(5'-3')；
The nucleotide sequence of the Sesn2 is as follows:
TGGCTGCCTGTGTGGGAGAGGAGTAAGGACCTCCAGGGACTAGCACTCCA is (such as SEQ ID NO:10 institute
Show) (5 ' -3 ').
Embodiment 2
This implementation provides the radiosensitive gene marker that screening obtains of embodiment 1 in identifying low LET ray radiation
Using.
Referring to fig. 4, expression fold difference of 10 genes after graded doses X-ray, carbon ion radiation exposure, heavy ion
Radiation exposure group is almost without radioreaction.
Referring to Fig. 5,10 genes are poor in graded doses X-ray, carbon ion radiation exposure 24 weeks gene expression values difference
It is different that there is statistical significance (P < 0.0001).
Referring to Fig. 6, Receiver operating curve (receiver operating characteristic curve,
ROC) figure, identification energy of average expression of 10 genes after graded doses X-ray, carbon ion radiation exposure to x-ray
Power.Area under the curve (Area under the Curve, AUC) is equal to 0.984,95% confidence interval (Confidence
Interval, CI) it is 0.952-1.000, and when above-mentioned 10 average expressions are equal to 1.033, identify X-ray sensitive
Degree 95.83%, specificity 100% shows that above-mentioned 10 gene mean expression values have good distinguishing ability to X-ray radiation.
The radiosensitive gene marker of the present invention is made into and whether is used to identify by the kit of low LET ray radiation, energy
It is enough quicker, convenient and it is accurate identify low LET ray and dosage reference be provided, facilitate marketization sale and use.
Embodiment described above is merely to illustrate technical idea and feature of the invention, in the art its object is to make
Technical staff it will be appreciated that the contents of the present invention and implement accordingly, patent model of the invention only cannot be limited with the present embodiment
It encloses, i.e., all disclosed spiritual, made same changes or modifications are still fallen in the scope of the patents of the invention.
Sequence table
<110>PLA Academy of Military Sciences's military medical research institute
<120>radiosensitive gene marker and the application in the low LET ray radiation of identification
<130> GAI18CN6324
<160> 10
<170> PatentIn version 3.5
<210> 1
<211> 50
<212> DNA
<213> Wnt7b
<400> 1
agagaggtgg ttagtggacc caggcagggc actggctgtc ccaatgctgt 50
<210> 2
<211> 50
<212> DNA
<213> Tprkb
<400> 2
gcgccaagtc tgcaaagcca ggtgctctca tagtgcagtt ctggggttgt 50
<210> 3
<211> 50
<212> DNA
<213> Pira1
<400> 3
ccaggatctg tgatcgcctc caaaagagca atgaccatct ggtgtcaggg 50
<210> 4
<211> 50
<212> DNA
<213> Pde4dip
<400> 4
ggggggaagg aactaatgac atcgtctcag acgttcatct ctaaccagcc 50
<210> 5
<211> 50
<212> DNA
<213> Limk2
<400> 5
tgagtatgct tgcactgtcc ccagcaagtg tgggagtggg gcctgcacta 50
<210> 6
<211> 50
<212> DNA
<213> Ctns
<400> 6
gccttcagaa ccaagtcctg ggggcttaga ggaccttgct tacctatgtc 50
<210> 7
<211> 50
<212> DNA
<213> Kcnk6
<400> 7
cagagcccaa gccacatcta ctactgtgtg cctagcacag aaaagcatgg 50
<210> 8
<211> 50
<212> DNA
<213> Csf2rb
<400> 8
tgagcacaca ttccaggtcc agtacaagaa gaaatcggac agctgggagg 50
<210> 9
<211> 50
<212> DNA
<213> Cd80
<400> 9
gctctttggg gcaggattcg gcgcagtaat aacagtcgtc gtcatcgttg 50
<210> 10
<211> 50
<212> DNA
<213> Sesn2
<400> 10
tggctgcctg tgtgggagag gagtaaggac ctccagggac tagcactcca 50
Claims (10)
1. radiosensitive gene marker, it is characterised in that: the radiosensitive gene marker include Wnt7b, Tprkb,
Pira1, Pde4dip, Limk2, Ctns, Kcnk6, Csf2rb, Cd80 and Sesn2.
2. radiosensitive gene marker according to claim 1, it is characterised in that:
The nucleotide sequence of the Wnt7b is as shown in SEQ ID NO:1；
The nucleotide sequence of the Tprkb is as shown in SEQ ID NO:2；
The nucleotide sequence of the Pira1 is as shown in SEQ ID NO:3；
The nucleotide sequence of the Pde4dip is as shown in SEQ ID NO:4；
The nucleotide sequence of the Limk2 is as shown in SEQ ID NO:5；
The nucleotide sequence of the Ctns is as shown in SEQ ID NO:6；
The nucleotide sequence of the Kcnk6 is as shown in SEQ ID NO:7；
The nucleotide sequence of the Csf2rb is as shown in SEQ ID NO:8；
The nucleotide sequence of the Cd80 is as shown in SEQ ID NO:9；
The nucleotide sequence of the Sesn2 is as shown in SEQ ID NO:10.
3. radiosensitive gene marker as claimed in claim 1 or 2 is identifying the application in low LET ray radiation.
4. application according to claim 3, which is characterized in that the application the following steps are included:
Detect radiosensitive gene marker Wnt7b, Tprkb in the organism that is radiated, Pira1, Pde4dip, Limk2,
The gene expression dose of Ctns, Kcnk6, Csf2rb, Cd80 and Sesn2, when significantly to a high-profile, then reflecting occurs in its expression
The organism that Que Ding do not radiated is the exposure of low LET ray radiation.
5. application according to claim 3 or 4, it is characterised in that: the low LET ray includes X-ray, β ray and γ
One of ray is a variety of.
6. application according to claim 3, it is characterised in that: the gene expression dose of the sensitive gene marker is it
The average value of transcriptional level differential expression multiple.
7. a kind of for whether identifying organism by the kit of low LET ray radiation, it is characterised in that: the kit contains
Radiosensitive gene marker as claimed in claim 1 or 2.
8. kit described in claim 7 is identifying the application in low LET ray radiation.
9. a kind of method for obtaining radiosensitive gene marker as claimed in claim 1 or 2 with non-treatment purpose, feature exist
In including the following steps:
After carrying out different ray types, the irradiation of various dose single graded doses and the irradiation of gradation graded doses to mouse, extract
Fresh lung tissue does genetic chip or real-time quantitative polymerase chain reaction, based on full-length genome gene expression arrays to 24 weeks lungs
Tissue full-length genome expression is analyzed, and analyzes different radiation exposures, the trend relationship of dose of radiation and gene expression obtains
It obtains gene expression amount to increase and increase with low LET ray radiation dosage, and does not change with high LET ray radiation doses change
Expressing gene combination, the i.e. radiosensitive gene marker.
10. according to the method described in claim 9, it is characterized by: the difference ray type includes low LET ray and height
LET ray；
Preferably, the high LET ray includes one of fast neutron ray, negative πmeson ray and Heavy ion beam or a variety of.
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