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  • R (particle, neutron)• T (Gonad)• DDREF (dose rate, dose fractionation)• A (Age)• G (Gender)• Modifying factor
14 :); '
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 !3968.//-10:;746%398+:,;<
NOTCH1• Clonal growth in youngtissue• Mutation of many
cancer-associatedgenes
TP53
in old tissue

Francesca D. Ciccarelli (2019) Nature 565, 301-303

 #"%• cell clones with mutational or epigenetic inactivation of the PTEN or INK4A
tumor suppressor genes are frequently found in histologically normal
endometria and breast (respectively) of cancer free women• the presence of TEL-AML1 and AML1-ETO translocations in blood cells ofnewborns is ~100-fold greater than the risk of the associated leukemias• most surprisingly, histologically advanced microscopic tumors are detected inmany tissues of adult humans but which appear to be mostly held in check by
unknown mechanisms.
• in frame Bcr-Abl fusions are detected in leukocytes of ~1 in 3 healthy individuals
the vast majority of which will fortunately never develop this leukemia

2$(22$#

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in vivo vs. in vitro!

In vivo exposure
CFU-S#$8 weekC3HBMIn vivo assayCFU-S

No. of colony (1106 cells injected)

1 weekIn vivo 1< 8
1W60

CFU-S40

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20In vitro 1 = 8

00

24Dose (Gy)6
Dose (Gy)'Ariyoshi et al. (2014) RR 181:302-313

#!$"!%
Pathway analysis
Pathway

5pValue*Chemokine receptors bind chemokines*

1.21E-05

Class A/1 (Rhodopsin-like receptors)

3.64E-05

Integrin cell surface interactions

9.79E-05

GPCR ligand binding

4.72E-04

Signaling by GPCR

6.33E-04

Cell surface interactions at the vascular wall

7.06E-04

TCR signaling

0.003455939

Signaling by Robo receptor

0.003610043

Peptide ligand-binding receptors

0.004250101

25

Fold change

Fgf120Infant (1w)

Adult (8w)

*

Csf24

Infant (1w)

Adult (8w)

0Gy0Gy321020

IL1b2Gy 6 2Gy 24

Infant (1w)

2Gy 6 2Gy 24

Adult (8w)

15

15
1010

5

500Gy

2Gy 6 2Gy 24

0Gy

2Gy 6 2Gy 24

00Gy

2Gy 6 2Gy 24

0Gy

2Gy 6 2Gy 24

Chemokine family genes, Csf2, Fgf1 and IL1b, all of which areradioprotective even treated post-irradiation, were found to increase postirradiation in only adult bone marrow tissues.

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