H27.11.

TCDD
[Biochemistry, 48, 5972-5983 (2009) ]

1.
2.
3.

1962

1.
TCDD
2. L.
3. P450


62
2,4-D
(41)

75

2,4,5-T
(44)

TCDD
(57)

1960

1970

(1945)

1980

1990

71

TCDD

(66)

2,4,5-T

(70)

(78)
83

(67)

(68)

62

2000

2010

(NAS)

62

AhR AhR

AhR

P450
1950

92

(04)

(76)
76

93
12
98

95

96

(04)

14

(11)
(79) (86)

20

103 KL

15

10

(67%)
2,4-D/2,4,5-T=1

: 9 KL

TCDD: 550 Kg
: 240 ha
480

1962
P450,

1964

1966

1968

1970

Nature, 422, 681-687 (2003)


O
CH2

N
H

a.

O
H

(IAA)

O
O

CH2

C
OH

CI

b.

CI

IAA , 2,4-D

(2,4-D)

O
O

CH2
CI

C
OH

CI
CI

(2,4,5-T)

IAA:
2,4-D:
Nature, 446, 621-622 (2007)

II

(Veteran and Agent Orange, 2012)


# 1968

# (PCB)

PCB
(PCDF)

1968
1968
1968
1968
1968
1968
1968
1968
1970
1970
1971
1972
1972
1973
1974

dead
dead
39
39
39
39
39
39
37
37
36
35
35
34
33

M
M
M
F
F
F
F
F
M
M
M
F
F
F
F

1980

1980

1981

1982

1983

1986

1989

1990

1990
1990

1990

1991

1992
1993
1996

27
27
26
25
24
21
18
17
17
17
17
16
15
14
11

F
F
M
F
F
M
F
M
M
M
F
M
F
F
M

Mizuno, R. et al. in Persistent organic pollutants research in Asia. P.411-415 (2008)

1976 7 10 (
) TCDD (30~130 kg)
(~1800 ha)

(1976)

(2005: , ), (2015: )

1976

1977

0
0
0
2
0
2
0
0
0
0
0
0
0
0
0
0

10
8
3
2
2
2
2
1
1
1
1
1
1
1
1
1

38
Bisanti, L. et al. 1980)

P450

, MC

P450

DNA

P450

TCDD

P450
DNA

P450
1. P450

B6
D2

, (+)

P450
P450

, (-)

2. B6 D2 B6 D2

; (+)
; (-)
(+)
(+)
(+) : (-) = 1:1
(+) : (-) = 3:1

B6 D2

[Kouri RE, et al. In Origins of human cancer, p818, (1978) ]

 TCDD
[3H]TCDD

[3H]-TCDD
TCDD ,
PCBs
B6 D2 B(a)P

1 nM [3H]-TCDD

+ 100 nM TCDD

[okey AB, et al. J. Biol. Chem. 254, 11636-11648 (1979) ]

[3H]TCDD B(a)P, PCBs

AhR

(AhR)

DNA

mRNA

RNA

AhR
2.4
32 2%

TCDD AhR

(TCDD,
)

AhR

( )

AhR

ARNT
ARNT

P450
DNA

(TNGCGTG)

mRNA

AhR

TCDD
(g/kg)
AhR+/+

AhR+/+
AhR-/-

40
40

(n) (%)

(n) (%)

(0)

3/23 (19)

38/38 (100)
0/28
(0)

33/38 (91)
0/28 (0)

0/23

Genes Cells, 2, 645-654 (1997)

(200 g 1
/
, 25 )

15/16 (94%)
0/10 (0%)
PNAS, 97, 779-782 (2000)

* ( ) 12.5 TCDD ,
TCDD 18.5 ,
AhR+/+
AhR AhR
AhR-/-

CI

CI

~ 940 : ,

CI

CI

1940 ~ :

2,3,7,8-TCDD

CH3
N=N

N
H

AhR

CH3

CH3
CH223191

TCDD

AhR

AHR2 lost?

400 380
300
200

410

450

AHR1/AHR2
510

AHR/AHRR

550

570
( )

600
490
440 420
360 300
540

CeAHR

Spineless

(
)(
)

(TCDD )

(CYP1)

AhR

AhR

(CYP1A1)

AhR

(IT ), ,
, ,
,

, ,
, , ,

, ,
, , ,

(1967)

(
)

NPO NGO


46

38

20

(
(24 )

5000

50

10

20
( 15 )

AhR

4.5
3.8
3
2

30
27

100

1000

(200

10
3

p8 (2005)

, , ,

AhR AhR DNA
AhR

AhR
AhR
AhR