Effects of Various Doses of 17.BETA.-estradiol on the Progression of Mammary Carcinomas Induced by Single and Multiple Administration of 7,12-Dimethylbenz[a]anthracene in Female Rats.

Omachi, Katsumi; Kawaguchi, Hiroaki; Funato, Mamoru; Sato, Kenichi; Okasaki, Keikou; Nagaoka, Takaharu; Abe, Syun-ichi; Yoshida, Hiroki

doi:10.1293/tox.13.67

Cited by 5 publications

(6 citation statements)

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“…These masses were localized in all areas (L1-6 and R1-6) of the mammary glands. MCs were briefly subclassified into papillary type, secretory type, ductal type, solid type or phyllodes type (like human phyllodes tumor) in this study, as described previously [5,12,16]. Phyllodes tumor is an uncommon biphasic breast tumor, with the ability to recur and metastasize, and it behaves biologically like a stromal neoplasm.…”

Section: Resultsmentioning

confidence: 99%

Effects of Fetal Exposure to Diethylstilbestrol on Mammary Tumorigenesis in Rats

Kawaguchi

Miyoshi

Miyamoto

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. The aim of this study was to investigate the effect of fetal exposure to diethylstilbestrol (DES) on the induction of mammary tumors induced by 7,12-dimethylbenz [a]anthracene (DMBA) in female rats. Pregnant rats were fed only normal diet, diet mixed with 0.1 ppm DES throughout pregnancy period or diet mixed with 0.1, 1 or 10 ppm DES from day 13 of pregnancy till the end of pregnancy. Delivered pups were given 10 mg DMBA by gastric intubation at 50 days after birth and observed till 336 days after birth. Some rats exposed to DES throughout pregnancy and those from day 13 till the end of pregnancy showed endocrine disrupting effects such as absence of CL and active lactation in mammary glands at necropsy, while no abnormal estrus cycle such as persistent estrus was seen during the observation period until 88 days after birth. Fetal exposure to 0.1 ppm DES throughout pregnancy period, 0.1 and 1 ppm DES from day 13 of pregnancy increased the incidence and number of mammary carcinomas (MCs) at the earlier period while exposure to 0.1 ppm DES throughout pregnancy period enhanced the incidence and number of benign proliferative lesions (PLs) at the later period. MCs appeared earlier than benign PLs. These results suggest that exposure to DES throughout pregnancy and from day 13 of pregnancy could induce endocrine disrupting conditions and enhance the induction of MCs and that exposure to DES throughout pregnancy enhance PLs. There is evidence that many environmental endocrine disruptors act as sex hormones, particularly during the perinatal or neonatal period, directly or indirectly affecting reproduction in human and rats [13,23,27]. Endogenous hormone mimics are proposed for a number of adverse human health effects, including infertility, abnormal prenatal and childhood development, and reproductive cancers [18].We have reported that the neonatal administration of diethylstilbestrol (DES) [12,14,33], 4-n-octylphenol [10], 17-estradiol (E 2 ) [4] and testosterone propionate [9,[28][29][30] affected mammary tumorigenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats.In humans, women exposed to diethylstilbestrol (DES), a synthetic estrogen with strong estrogenic activity, during pregnancy have a moderately increased risk of breast cancer [17,27]. It is also known that the frequency of vaginal clear cell adenocarcinoma was increased in young women whose mothers used DES to prevent or lower the risk of abortion, while DES was ineffective to prevent miscarriages and premature births [3,27].Huggins et al. previously showed that a single administration of 20 mg DMBA at 50 days after birth induced visible mammary cancer in rats by 110 days after birth [6]. This animal has since been a useful model for studying the carcinogenesis of human breast cancer. DMBA is known to be a polycyclic hydrocarbon carcinogen forming DNA adducts [24]. The presence of estrogen and progesterone receptors in DMBA-induced mammary carcinomas (MCs) has been well documented in rats [31,32]. DMBA-transformed cells (intrad...

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Section: Resultsmentioning

confidence: 99%

Effects of Fetal Exposure to Diethylstilbestrol on Mammary Tumorigenesis in Rats

Kawaguchi

Miyoshi

Miyamoto

et al. 2009

The Journal of Veterinary Medical Science

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“…To visualize the immunoreactivity, 3,3′-diaminobenzidine tetrachloride (DAB)-containing 0.02% hydrogen peroxide was used. The sections were then washed, counter-stained, dehydrated, cleared in xylene, and mounted (Kawaguchi et al, 2000; Okasaki et al, 1998; Omachi et al, 2000). For Ki-67, nuclear stained cells were interpreted as positive cells.…”

Section: Methodsmentioning

confidence: 99%

Effects of Neonatally Administered Diethylstilbestrol on Induction of Mammary Carcinomas Induced by 7, 12-Dimethylbenz[A]Anthracene in Female Rats

et al. 2007

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Various doses of diethylstilbestrol (DES) were administered to rats once at birth. Thereafter, at 50 days after birth, the rats in all groups were given 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA) and undergone necropsy at 300 days after birth. The incidence of mammary carcinomas (MCs) were 50, 54, 91, 39, 19% at 175 days after birth, and 77, 87, 100, 85, 75% at necropsy in the 0, 0.1, 1, 10, 100 microg groups, respectively. The incidence of rats without corpus luteum were 0, 0, 0, 30, 100% at 50 days after birth, and 0, 40, 53, 93, 100% at necropsy in the 0, 0.1, 1, 10, 100 microg groups, respectively. Observation of the whole mount specimens showed a higher number of terminal end buds (TEBs) in the 1 microg group and a lower number in the 100 microg group compared with the control at 50 days after birth. It suggested that the administration of a relatively low dose (1 microg) of DES during neonatal period may increase TEBs, thus resulting in a stimulatory effect on the initiation of MCs.

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“…MCs were briefly subclassified into papillary type, solid type, or secretory type in this study as described previously. 6,11 PLs consisted of solid masses, which included fibroadenoma and lobular hyperplasia, and gross cysts in this study. Fibroadenoma, by far the most common benign neoplasm of the rat mammary gland, 2 consisted of rich hyalinized stroma and developed alveoli (Fig.…”

Section: Pathology Of Mammary Masses Induced By Dmba (Experiments A)mentioning

confidence: 99%

Effects of Neonatally Administered High-dose Diethylstilbestrol on the Induction of Mammary Tumors Induced by 7,12-Dimethylbenz[a]anthracene in Female Rats

Kawaguchi¹,

Umekita²,

Souda³

et al. 2009

Vet Pathol

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Abstract. The aim of this study was to investigate the effects of neonatal administration of a relatively high dose of diethylstilbestrol (DES) on the induction of mammary carcinomas (MCs) and benign proliferative lesions (PLs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Three different terms of daily administration of DES (10 mg) were used: 0-14, 0-5, and 6-14 days after birth. Control animals were administered solvent (oil) alone once daily from 0 to 14 days after birth. Rats were given DMBA (10 mg) at 50 days after birth. All rats administered DES showed persistent estrus and anovulatory ovaries. In rats administered DES from 0 to 14 and 0 to 5 days after birth there was protection from development of MCs and PLs, and serum levels of both estrogen and progesterone were significantly lower than in the control animals at 100 days after birth. In rats administered DES from 6 to 14 days after birth, the incidence of MCs was equal to that of the control animals (100%), and the number of PLs was significantly higher than in the control animals. The critical period for exposure to endocrine disruptors, such as DES, affecting the induction of MCs and PLs may be from 0 to 5 days after birth.

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Effects of Various Doses of 17.BETA.-estradiol on the Progression of Mammary Carcinomas Induced by Single and Multiple Administration of 7,12-Dimethylbenz[a]anthracene in Female Rats.

Cited by 5 publications

References 18 publications

Effects of Fetal Exposure to Diethylstilbestrol on Mammary Tumorigenesis in Rats

Effects of Fetal Exposure to Diethylstilbestrol on Mammary Tumorigenesis in Rats

Effects of Neonatally Administered Diethylstilbestrol on Induction of Mammary Carcinomas Induced by 7, 12-Dimethylbenz[A]Anthracene in Female Rats

Effects of Neonatally Administered High-dose Diethylstilbestrol on the Induction of Mammary Tumors Induced by 7,12-Dimethylbenz[a]anthracene in Female Rats

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