Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters

Hilakivi-Clarke, Leena

doi:10.1186/bcr3649

Breast Cancer Research

Table 1 Summary of results on mammary gland development and mammary tumorigenesis obtained in mice and rats exposed to diethylstilbestrol in utero, at birth, during neonatal period (between days 0 and 5) or postnatally

From: Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters

Reference	Model	DES dose (total)	Time of administration	Effect on reproductive system^a	Effect on mammary gland or mammary cancer
Effects on mammary gland
Nagasawa et al. 1978 [12]	Balb/cfC3H mice	5 μg	0-5 Postnatal	100% no CL	Hyperplasia↑
Nagasawa et al. 1978 [12]	Balb/cfC3H mice	20 μg	0-5 Postnatal	100% no CL	Hyperplasia↑
Boylan 1978 [13]	Rat	1.2 μg	Week 2 G	Percentage live deliveries: 97/F¹ 94%	Normal
		12 μg	Week 2 G	50%	Normal
		60 μg	Week 2 G	27%	Normal
		120 μg	Week 2 G	33%	Normal
		1,200 μg	Week 2 G	No surviving pups
		12,000 μg	Week 2 G	No surviving pups	Normal
		1.2 μg	Week 3 G	81/F¹ 78%	Slightly enlarged nipples
		120 μg	Week 3 G	62/F¹ 57%
		12,000 μg	Week 3 G	No surviving pups
Bern et al. 1987 [14]	Balb/c mice	5 × 10^-5 μg	0-5 Postnatal	Cervicovaginal lesions12%, 65% no CL	HANs 10%
		5 × 10^-4 μg	0-5 Postnatal	19%, 88% no CL	HANs 19%
		5 × 10^-3 μg	0-5 Postnatal	42%, 95% no CL	HANs 41%
		5 × 10^-2 μg	0-5 Postnatal	63%, 100% no CL	HANs 7%
		5 × 1 μg	0-5 Postnatal	80%, 100% no CL	HANs 12%
Vassilacopoulou and Boylan 1993 [15]	ACI rat	4 + 4 μg	15 + 18 G	Not studied	Hypodifferentiation and hyperproliferation
Effect on mammary tumorigenesis
Boylan and Calhoon 1979 [16]	Rat/DMBA	1.2 μg	Week 2 G	Not studied	Multiplicity↑
Boylan and Calhoon 1979 [16]	Rat/DMBA	1.2 μg	Week 3 G	Not studied	Multiplicity↑
Boylan and Calhoon 1983 [18]	Rat/DMBA	0.6 + 0.6 μg	15 + 18 G	Not studied	Incidence + multiplicity↑
Rothschild et al. 1987 [19]	ACI rat	0.4 + 0.4 μg	15 + 18 G	Not studied	No change
Rothschild et al. 1987 [19]	ACI rat	4 + 4 μg	15 + 18 G	Not studied	Incidence↑
Ninomiya et al. 2007 [20]	Rat/DMBA	0.1 μg	Birth (one dose)	Normal cycle, 40% CL	Multiplicity↑
		1 μg	Birth (one dose)	19% PE, 50% CL, U w↓	Incidence + multiplicity↑
		10 μg	Birth (one dose)	77% PE, 92% CL, U w↓	Multiplicity↑
		100 μg	Birth (one dose)	100% PE, 100% CL, O + U w↓	No change
Yoshikawa et al. 2008 [22]	Rat/DMBA	14 x 1 μg	0-14 Postnatal	100% PE, no CL, O + U w↓, E2 and P↓	Incidence↓
		5 x 1 μg	0-5	PE, no CL, O + U w↓, E2 and P↓	Incidence↓
		9 x 1 μg	6-14	PE, no CL, O + U w↓	No change
Kawaguchi et al. 2009 [21]	Rat/DMBA	0.1 ppm	0-21 G	Few surviving pups
		1 ppm	0-21 G	No surviving pups
		10 ppm	0-21 G	No surviving pups	(Assessed 10 weeks after
		100 ppm	0-21 G	No surviving pups	DMBA exposure):
		0.1 ppm	13-21 G	11% no CL	Incidence + multiplicity↑
		1 ppm	13-21 G	30% no CL	Incidence + multiplicity↑
		10 ppm	13-21 G	Very few surviving pups	Incidence↑
		100 ppm	13-21 G	No surviving pups

^aIn control mice, corpora lutea (CL) is present in about 31 to 36% of adults, whilst in control rats it is present in 100% of adult animals. DES, diethylstilbestrol; DMBA, dimethylbenz[a]antracene; E2, estradiol; F¹, F1 generation; G, gestation; HAN, hyperplastic alveolar nodule; O, ovary; P, progesterone; PE, persistent estrus; U, uterus; w, weight.

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