厚生科学研究「畜水産食品中残留ホルモンのヒト健康に及ぼす影響に関する研究」

表　17β－エストラジオールの遺伝毒性

Test system Result 　 Dose Reference

　 Without
exogenous
matabolic
system With
exogenous
matabolic
system (LED or HID)
ug/ml or mg/kg 　

Salmonella typhimurium TA100, TA1535, TA1537, TA1538, TA98, reverse mutation - - 2500 ug/plate Lang & Redman (1979)

Salmonella typhimurium TA1535, TA1537, TA1538, reverse mutation - - 500 ug/plate Ingerowski et al. (1981)

Salmonella typhimurium TA100, TA1535, TA1537, TA1538, TA98, reverse mutation - - 500 ug/plate Lang & Reimann (1993)

Salmonella typhimurium TA100, TA1535, TA1537, TA1538, TA98, reverse mutation - - 5000ug/plate Richold (1988)

DNA strand breaks, cross-links or related damage, mouse brain DNA in vitro (+) NT 27.2 Yamafuji et al. (1971)

DNA strand breaks, cross-links or related damage, Chinese hamster V79 DNA in vitro - - 816 Swenberg (1981)

DNA single-strand breaks, rat hepatocytes in vitro - NT 82 Sina et al. (1983)

DNA repair exclusive of unscheduled DNA synthesis, female C57BL mouse mammary epithelial cells in vitro - NT 0.2 Telang et al. (1992)

Unscheduled DNA synthesis, Syrian hamster embryo cells in vtro - NT 10 Tsutsui et al. (1987)

Gene mutation, Chinese hamster lung V79 cells, hprt locus in vitro - - 27.2 Drevon et al. (1981)

Gene mutation, Chinese hamster lung V79 cells, ouabain in vitro - - 27.2 Drevon et al. (1981)

Gene mutation, Syrian hamster embryo cells, hprt and Na+/K+ ATPase loci in vitro - NT 10 Tsutsui et al. (1987)

Gene mutation, Chinese hamster lung V79 cells, hprt locus in vitro + - 10-10M Rajah & Pento (1995)

Gene mutation, Mouse lymphoma L5178Y cells, tk locus in vitro - - 255, 174ug/ml Richold (1988)

Gene mutation, human breast cancer MCF-7 cells, MTXr in vitro + - 10-8M Thibodeau et al. (1998)

Sister chromatid exchange, mouse cervical fibroblasts and kindney cells in vitro - NT 2.7 Hillbertz-Nilsson & Rorsberg (1985)

Sister chromatid exchange, Syrian hamste embryo cells in vitro - NT 10 Tsutsui et al. (1987)

Micronucleus formation, Syrian hamster embryo cells in vitro +** NT 2.72 Schnitzler et al. (1994)

Micronucleus formation, Chinese hamster lung V79 cells in vitro +** NT 20x10-6M Eckert and Stopper (1996)

Micronucleus formation, ovine seminal vesicle cells in vitro +** NT 2.72 Schnitzler et al. (1994)

Chromosomal aberration, Syrian hamster embryo cells in vitro - NT 10 Tsutsui et al. (1987)

Chromosomal aberration, Syrian hamster embryo cells in vitro - NT 8.17 Tsutsui et al. (1987)

Chromosomal aberrations, Chinese hamster lung V79 cells in vitro + 　 3x10-5M Sato et al (1992)

Aneuploidy, male Chinese hamster DON cells in vitro + NT 13.6 Wheeler et al. (1986)

Test system Result 　 Dose Reference

　 Without
exogenous
matabolic
system With
exogenous
matabolic
system (LED or HID)
ug/ml or mg/kg 　

Aneuploidy, Syrian hamster embryo cells in vitro + NT 10 Tsutsui et al. (1987, 1990)

Aneuploidy, Syrian hamster embryo cells in vitro + NT 0.82 Tsutsui et al. (1997)

Cell transformation, BALB/c3T3 embryo-derived mouse fibroblasts + NT 5.5 Liehr et al. (1987a)

Cell transformation, C3H 10T1/2 mouse cells + NT 0.27 Kennedy & Weichselbaum (1981)

Cell transformation, Syrian hamster embryo cells + NT 3 Tsutsui et al. (1987)

Cell transformation, Syrian hamster embryo cells NT + 3 Hayashi et al. (1996)

Cell transformation, Syrian hamster embryo cells + NT 2.72 Tsutsui et al. (1997)

Cell transformation, female C57BL mouse mammary epithelial cells - NT 0.2 Telang et al. (1992)

Cell transformation, primary baby rat kedney + HPV16 + ras - NT 0.27 Pater et al. (1990)

Sister chromatid exchange, human lymphocytes in vitro - NT 13.6 Hill & Wolff (1983)

Sister chromatid exchange, human lymphocytes in vitro - - 27.2 Banduhn & Obe (1985)

Micronucleus formation, human lymphocytes in vitro + NT 1.3 Banduhn & Obe (1985)

Chromosomal aberration, human lymphocytes in vitro - NT 100 Stenchever et al. (1969)

Chromosomal aberration, human lymphocytes in vitro - - 27.2 Banduhn & Obe (1985)

Aneuploidy, human lymphocytes in vitro (+) NT 13.6 Banduhn & Obe (1985)

Aneuploidy, human foreskin JHU-1 fibroblasts in vitro + NT 20 Tsutsui et al. (1990)

Microtuble disruption, human breast cancer MCF-7 and MDA-MB-231 cells, MTXr in vitro + 　 50 uM Aizu-Yokota et al, (1994)

DNA strand breaks, cross-links or related damage, male Syrian hamster kidney and liver in vivo (+) 　 22.5 mg impx1, 2wk Han & Liehr (1994)

DNA strand breaks, cross-links or related damage, male Syrian hamster kidney in vivo + 　 250 mg/d impx1, 7d Han & Liehr (1994)

DNA strand breaks, cross-links or related damage, male Syrian hamster liver in vivo - 　 250 mg/d impx1, 7d Han & Liehr (1994)

DNA strand breaks, cross-links or related damage, male Syrian hamster kidney and liver in vivo - 　 150 ipx1 Han & Liehr (1994)

Sister chromatid exchange, female NMRI mouse uterine cervix and uterine horn epithelial cells in vivo + 　 5 ug scx1 Forsberg (1991)

Sister chromatid exchange, female NMRI kidney cells in vivo - 　 5 ug scx1 Forsberg (1991)

Chromosomal aberrations, male Syrian hamster renal cortical cells in vivo + 　 125 ug/d impx1, 5 ml Banerjee et al. (1994)

Chromosomal aberrations, Rat bone marrow and spermatogonia in vivo - 　 100mg/kg Richold (1988)

Test system Result 　 Dose* Reference

　 Without
exogenous
matabolic
system With
exogenous
matabolic
system (LED or HID)
ug/ml or mg/kg 　

Micronucleus formation, B6C3F1 mouse and F344 rat bone marrow, in vivo - 　 1250 mg/kg Shelby et al. (1997)

Micronucleus formation, CBA mouse bone marrow, in vivo - 　 0.02 mg/kg Ashby et al. (1997)

Micronucleus formation, AP rat bone marrow, in vivo - 　 150 mg/kg Ashby et al. (1997)

Micronucleus formation, BDF1 & CD-1 mouse peripheral blood, in vivo - 　 2000mg/kg Morita et al. (1997)

Micronucleus formation, Swiss albino mouse bone marrow, in vivo + 　 0.1mg/kg Dhillon & Dhillon (1995)

Microsatellite instability, Syrian hamster, estrogen induced kidney tumor cells, in vivo + 　 25 mg, impx2, 6mo Hodgson et al. (1998)

Aneuploidy, female NMRI mouse uterine cervix and uterine horn epithelial cells in vivo - 　 5 ug scx1 Forsberg (1991)

Aneuploidy, female NMRI mouse kidney cells in vivo - 　 5 ug scx1 Forsberg (1991)

Aneuploidy, male Syrian hamster renal tubular cells in vivo + 　 20 mg impx1, 3.5 mo Li et al. (1993)

Increase in nuclear DNA content (aneuploidy), female BALB/c mouse cervicovaginal epithelium in vivo + 　 25 ug scx5 Hajek et al. (1993)

IARC (1999)を一部改変，追加
*結果が陽性の場合は最小有効用量(LED)を，結果が陰性の場合は最大無作用量(HID)を示す
**動原体を持つ小核が41-73%出現している

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Test system	Result		Dose	Reference
	Without exogenous matabolic system	With exogenous matabolic system	(LED or HID) ug/ml or mg/kg
Salmonella typhimurium TA100, TA1535, TA1537, TA1538, TA98, reverse mutation	-	-	2500 ug/plate	Lang & Redman (1979)
Salmonella typhimurium TA1535, TA1537, TA1538, reverse mutation	-	-	500 ug/plate	Ingerowski et al. (1981)
Salmonella typhimurium TA100, TA1535, TA1537, TA1538, TA98, reverse mutation	-	-	500 ug/plate	Lang & Reimann (1993)
Salmonella typhimurium TA100, TA1535, TA1537, TA1538, TA98, reverse mutation	-	-	5000ug/plate	Richold (1988)
DNA strand breaks, cross-links or related damage, mouse brain DNA in vitro	(+)	NT	27.2	Yamafuji et al. (1971)
DNA strand breaks, cross-links or related damage, Chinese hamster V79 DNA in vitro	-	-	816	Swenberg (1981)
DNA single-strand breaks, rat hepatocytes in vitro	-	NT	82	Sina et al. (1983)
DNA repair exclusive of unscheduled DNA synthesis, female C57BL mouse mammary epithelial cells in vitro	-	NT	0.2	Telang et al. (1992)
Unscheduled DNA synthesis, Syrian hamster embryo cells in vtro	-	NT	10	Tsutsui et al. (1987)
Gene mutation, Chinese hamster lung V79 cells, hprt locus in vitro	-	-	27.2	Drevon et al. (1981)
Gene mutation, Chinese hamster lung V79 cells, ouabain in vitro	-	-	27.2	Drevon et al. (1981)
Gene mutation, Syrian hamster embryo cells, hprt and Na+/K+ ATPase loci in vitro	-	NT	10	Tsutsui et al. (1987)
Gene mutation, Chinese hamster lung V79 cells, hprt locus in vitro	+	-	10-10M	Rajah & Pento (1995)
Gene mutation, Mouse lymphoma L5178Y cells, tk locus in vitro	-	-	255, 174ug/ml	Richold (1988)
Gene mutation, human breast cancer MCF-7 cells, MTXr in vitro	+	-	10-8M	Thibodeau et al. (1998)
Sister chromatid exchange, mouse cervical fibroblasts and kindney cells in vitro	-	NT	2.7	Hillbertz-Nilsson & Rorsberg (1985)
Sister chromatid exchange, Syrian hamste embryo cells in vitro	-	NT	10	Tsutsui et al. (1987)
Micronucleus formation, Syrian hamster embryo cells in vitro	+**	NT	2.72	Schnitzler et al. (1994)
Micronucleus formation, Chinese hamster lung V79 cells in vitro	+**	NT	20x10-6M	Eckert and Stopper (1996)
Micronucleus formation, ovine seminal vesicle cells in vitro	+**	NT	2.72	Schnitzler et al. (1994)
Chromosomal aberration, Syrian hamster embryo cells in vitro	-	NT	10	Tsutsui et al. (1987)
Chromosomal aberration, Syrian hamster embryo cells in vitro	-	NT	8.17	Tsutsui et al. (1987)
Chromosomal aberrations, Chinese hamster lung V79 cells in vitro	+		3x10-5M	Sato et al (1992)
Aneuploidy, male Chinese hamster DON cells in vitro	+	NT	13.6	Wheeler et al. (1986)
Test system	Result		Dose	Reference
	Without exogenous matabolic system	With exogenous matabolic system	(LED or HID) ug/ml or mg/kg
Aneuploidy, Syrian hamster embryo cells in vitro	+	NT	10	Tsutsui et al. (1987, 1990)
Aneuploidy, Syrian hamster embryo cells in vitro	+	NT	0.82	Tsutsui et al. (1997)
Cell transformation, BALB/c3T3 embryo-derived mouse fibroblasts	+	NT	5.5	Liehr et al. (1987a)
Cell transformation, C3H 10T1/2 mouse cells	+	NT	0.27	Kennedy & Weichselbaum (1981)
Cell transformation, Syrian hamster embryo cells	+	NT	3	Tsutsui et al. (1987)
Cell transformation, Syrian hamster embryo cells	NT	+	3	Hayashi et al. (1996)
Cell transformation, Syrian hamster embryo cells	+	NT	2.72	Tsutsui et al. (1997)
Cell transformation, female C57BL mouse mammary epithelial cells	-	NT	0.2	Telang et al. (1992)
Cell transformation, primary baby rat kedney + HPV16 + ras	-	NT	0.27	Pater et al. (1990)
Sister chromatid exchange, human lymphocytes in vitro	-	NT	13.6	Hill & Wolff (1983)
Sister chromatid exchange, human lymphocytes in vitro	-	-	27.2	Banduhn & Obe (1985)
Micronucleus formation, human lymphocytes in vitro	+	NT	1.3	Banduhn & Obe (1985)
Chromosomal aberration, human lymphocytes in vitro	-	NT	100	Stenchever et al. (1969)
Chromosomal aberration, human lymphocytes in vitro	-	-	27.2	Banduhn & Obe (1985)
Aneuploidy, human lymphocytes in vitro	(+)	NT	13.6	Banduhn & Obe (1985)
Aneuploidy, human foreskin JHU-1 fibroblasts in vitro	+	NT	20	Tsutsui et al. (1990)
Microtuble disruption, human breast cancer MCF-7 and MDA-MB-231 cells, MTXr in vitro	+		50 uM	Aizu-Yokota et al, (1994)
DNA strand breaks, cross-links or related damage, male Syrian hamster kidney and liver in vivo	(+)		22.5 mg impx1, 2wk	Han & Liehr (1994)
DNA strand breaks, cross-links or related damage, male Syrian hamster kidney in vivo	+		250 mg/d impx1, 7d	Han & Liehr (1994)
DNA strand breaks, cross-links or related damage, male Syrian hamster liver in vivo	-		250 mg/d impx1, 7d	Han & Liehr (1994)
DNA strand breaks, cross-links or related damage, male Syrian hamster kidney and liver in vivo	-		150 ipx1	Han & Liehr (1994)
Sister chromatid exchange, female NMRI mouse uterine cervix and uterine horn epithelial cells in vivo	+		5 ug scx1	Forsberg (1991)
Sister chromatid exchange, female NMRI kidney cells in vivo	-		5 ug scx1	Forsberg (1991)
Chromosomal aberrations, male Syrian hamster renal cortical cells in vivo	+		125 ug/d impx1, 5 ml	Banerjee et al. (1994)
Chromosomal aberrations, Rat bone marrow and spermatogonia in vivo	-		100mg/kg	Richold (1988)
Test system	Result		Dose*	Reference
	Without exogenous matabolic system	With exogenous matabolic system	(LED or HID) ug/ml or mg/kg
Micronucleus formation, B6C3F1 mouse and F344 rat bone marrow, in vivo	-		1250 mg/kg	Shelby et al. (1997)
Micronucleus formation, CBA mouse bone marrow, in vivo	-		0.02 mg/kg	Ashby et al. (1997)
Micronucleus formation, AP rat bone marrow, in vivo	-		150 mg/kg	Ashby et al. (1997)
Micronucleus formation, BDF1 & CD-1 mouse peripheral blood, in vivo	-		2000mg/kg	Morita et al. (1997)
Micronucleus formation, Swiss albino mouse bone marrow, in vivo	+		0.1mg/kg	Dhillon & Dhillon (1995)
Microsatellite instability, Syrian hamster, estrogen induced kidney tumor cells, in vivo	+		25 mg, impx2, 6mo	Hodgson et al. (1998)
Aneuploidy, female NMRI mouse uterine cervix and uterine horn epithelial cells in vivo	-		5 ug scx1	Forsberg (1991)
Aneuploidy, female NMRI mouse kidney cells in vivo	-		5 ug scx1	Forsberg (1991)
Aneuploidy, male Syrian hamster renal tubular cells in vivo	+		20 mg impx1, 3.5 mo	Li et al. (1993)
Increase in nuclear DNA content (aneuploidy), female BALB/c mouse cervicovaginal epithelium in vivo	+		25 ug scx5	Hajek et al. (1993)