Persistent Abnormalities in the Rat Mammary Gland following Gestational and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)

Fenton, Suzanne E.; Hamm, Jon; Birnbaum, Linda S.; Youngblood, Geri L.

doi:10.1093/toxsci/67.1.63

Cited by 151 publications

(149 citation statements)

References 44 publications

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“…Estrogens are critical to the proliferation of breast tissue and development of the mammary gland, and early age of menarche, as well as late menopause, and late age at first birth are proxies for estrogen burden and known risk factors for breast cancer. [99][100][101] Early environmental exposures that mimic estrogens, such as bisphenol A, 102 atrazine, 103 and polyaromatic hydrocarbons, 104 may be related to earlier breast development, thereby putting the rapidly proliferating mammary tissue at risk. Chemicals that are associated with early menarche, such as polybrominated biphenyls 105 and dichlorodiphenyldichloroethylene, 106 are also of interest.…”

Section: Breast Cancermentioning

confidence: 99%

“…104,107,109 Toxicologic studies show that dosing with endocrinedisrupting chemicals during different periods in an animal's life produces different effects on the mammary gland and hormone levels. 102,103,110 The importance of early exposure is illustrated by data from women who were exposed to radiation from the atomic bomb in Hiroshima. Girls at highest risk for breast cancer (ninefold increased risk) were those who were aged Յ4 years at the time of the bomb blast.…”

Section: Breast Cancermentioning

confidence: 99%

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Public Health Implications of Altered Puberty Timing

et al. 2008

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Changes in puberty timing have implications for the treatment of individual children, for the risk of later adult disease, and for chemical testing and risk assessment for the population. Children with early puberty are at a risk for accelerated skeletal maturation and short adult height, early sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated with an increased risk for testicular cancer according to several, but not all, epidemiologic studies. Girls and, possibly, boys who exhibit premature adrenarche are at a higher risk for developing features of metabolic syndrome, including obesity, type 2 diabetes, and cardiovascular disease later in adulthood. Altered timing of puberty also has implications for behavioral disorders. For example, an early maturation is associated with a greater incidence of conduct and behavior disorders during adolescence. Finally, altered puberty timing is considered an adverse effect in reproductive toxicity risk assessment for chemicals. Recent US legislation has mandated improved chemical testing approaches for protecting children's health and screening for endocrinedisrupting agents, which has led to changes in the US Environmental Protection Agency's risk assessment and toxicity testing guidelines to include puberty-related assessments and to the validation of pubertal male and female rat assays for endocrine screening.

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Section: Breast Cancermentioning

confidence: 99%

Section: Breast Cancermentioning

confidence: 99%

Public Health Implications of Altered Puberty Timing

et al. 2008

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“…There have been reported gross malformations of the external genitalia of female rat offspring exposed to TCDD in utero [7]. Female rats exposed perinatally to TCDD weighed significantly less than the control rats and displayed delayed vaginal opening and persistent vaginal threads [8]. Our lab has shown that prenatal TCDD treatment can have carcinogenic consequences in the mammary gland, another hormone-responsive organ.…”

Section: 378-tetrachlorodibenzo-p-dioxin (Tcdd)mentioning

confidence: 79%

“…In that study, an increased number of terminal end buds, a proliferative, immature structure that is susceptible to carcinogenesis, were observed at the time of DMBA exposure in TCDD-exposed animals, suggesting that TCDD delayed mammary gland maturation. Other investigators have noted that mammary glands taken from 4-day-old offspring exposed perinatally to TCDD had reduced primary branches, decreased epithelial elongation, and significantly fewer alveolar buds and lateral branches [8]. Though control animals developed well-differentiated terminal structures by postnatal day 68, TCDD-exposed animals retained undifferentiated terminal structures.…”

Section: 378-tetrachlorodibenzo-p-dioxin (Tcdd)mentioning

confidence: 93%

Prenatal TCDD Exposure Delays Differentiation and Alters Cell Proliferation and Apoptosis in the Uterus of the Sprague-Dawley Rat

Whitsett¹,

Kalia²,

Eltoum³

et al. 2008

TOTOXIJ

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine-disrupting chemical that alters cellular organization at both macroscopic and molecular levels. Our goal was to determine the effects that prenatal TCDD exposure has on uterine morphology, cell proliferation, apoptosis, and protein expression. Pregnant Sprague-Dawley rats were treated with 3 μg TCDD/kg body weight by gavage on gestational day 15. At 50 days postpartum, female offspring exposed in utero to TCDD displayed uteri that were atrophic in appearance, but with a 2-fold significant increase in luminal epithelial cell proliferation and a significant decrease in apoptosis (10-and 4-fold in glandular and luminal epithelium, respectively), compared to the controls. Epidermal growth factor receptor (EGFR) was significantly increased and superoxide dismutase 1 (SOD1) was significantly decreased in uteri of rats exposed prenatally to TCDD. We conclude that TCDD can inhibit maturation and modulate uterine proteins that are known to play a role in uterine growth as well as alter epithelial cell proliferation and apoptosis in a manner that may enhance disease, including carcinogenesis.

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“…Rats exposed to a single dose of TCDD on gestation day 15 retained undifferentiated terminal structures on post-natal day 68 (Fenton et al, 2002). Exposure effects of dioxin include delayed proliferation and differentiation of the mammary gland as well as an elongation of the window of sensitivity to potential carcinogens (Birnbaum and Fenton, 2003).…”

Section: Dioxinmentioning

confidence: 99%

Chronic diseases and early exposure to airborne mixtures: Part III. Potential origin of pre-menopausal breast cancers

Argo¹

2009

J Expo Sci Environ Epidemiol

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This is the third in a series dealing with chronic diseases and early exposure to airborne mixtures from industrial releases. The purpose of this study is to increase the understanding of previously unconsidered factors in the physical environment potentially acting as risk factors for female breast cancer. Data are from the Environmental Quality Database containing lifetime residential records for about 20,000 cases, with 1 of 15 cancers and about 5000 controls. Subjects resided within 25 km of all kraft mills, sulfite mills, coke ovens, oil refineries, copper, nickel and lead/zinc smelters operating in Canada in [1967][1968][1969][1970], and were aged o31 years. Subjects are exposed at home to simultaneous counter-current plumes of dioxin congeners and dimethyl sulfate (DMS) during the exposure period. DMS concentration increases with time of flight from the source and [SO 2 ] at 2 km. For all source types the number of cancers in an age cohort declines as the age of the cohort increases. The number of cases less than the median distance is less than the number of cases greater than the median distance. This supports the presence of a new source of risk with an origin in the plume. The crude rate of breast cancer, averaged over the 25 km of the study area for each age cohort o31 years of age, as well as source type, is least when the conditions of initial exposure are [SO 2 ]Z[DMS] and increases as [DMS] increases. The probability of an adverse effect from early, intermittent and simultaneous exposure to Dioxin and DMS, manifesting as a breast cancer after a latency period of as little as 26 years, is a function of age of first exposure, distance from the source and source type. The most susceptible age cohorts are the youngest.

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Persistent Abnormalities in the Rat Mammary Gland following Gestational and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)

Cited by 151 publications

References 44 publications

Public Health Implications of Altered Puberty Timing

Public Health Implications of Altered Puberty Timing

Prenatal TCDD Exposure Delays Differentiation and Alters Cell Proliferation and Apoptosis in the Uterus of the Sprague-Dawley Rat

Chronic diseases and early exposure to airborne mixtures: Part III. Potential origin of pre-menopausal breast cancers

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