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Maternal dioxin exposure combined with a diet high in fat increases mammary cancer incidence in mice.
- Source :
-
Environmental health perspectives [Environ Health Perspect] 2010 May; Vol. 118 (5), pp. 596-601. - Publication Year :
- 2010
-
Abstract
- Background: RESULTS from previous studies have suggested that breast cancer risk correlates with total lifetime exposure to estrogens and that early-life 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or diets high in fat can also increase cancer risk.<br />Objectives: Because both TCDD and diet affect the estrogen pathway, we examined how TCDD and a high-fat diet (HFD) interact to alter breast cancer susceptibility.<br />Methods: We exposed pregnant female FVB/NJ mice (12.5 days postcoitus) to 1 microg/kg TCDD or vehicle; at parturition, the dams were randomly assigned to a low-fat diet (LFD) or a high-fat diet (HFD). Female offspring were maintained on the same diets after weaning and were exposed to 7,12-dimethylbenz[a]anthracene on postnatal days (PNDs) 35, 49, and 63 to initiate mammary tumors. A second cohort of females was treated identically until PND35 or PND49, when mammary gland morphology was examined, or PND50, when mammary gland mRNA was analyzed.<br />Results: We found that maternal TCDD exposure doubled mammary tumor incidence only in mice fed the HFD. Among HFD-fed mice, maternal TCDD exposure caused rapid mammary development with increased Cyp1b1 (cytochrome P450 1B1) expression and decreased Comt (catechol-O-methyltransferase) expression in mammary tissue. Maternal TCDD exposure also increased mammary tumor Cyp1b1 expression.<br />Conclusions: Our data suggest that the HFD increases sensitivity to maternal TCDD exposure, resulting in increased breast cancer incidence, by changing metabolism capability. These results provide a mechanism to explain epidemiological data linking early-life TCDD exposure and diets high in fat to increased risk for breast cancer in humans.
- Subjects :
- Animals
Aryl Hydrocarbon Hydroxylases genetics
Catechol O-Methyltransferase genetics
Cocarcinogenesis
Cytochrome P-450 CYP1B1
Dietary Fats administration & dosage
Environmental Pollutants administration & dosage
Environmental Pollutants toxicity
Estrogens, Non-Steroidal administration & dosage
Estrogens, Non-Steroidal toxicity
Female
Gene Expression drug effects
Humans
Mammary Neoplasms, Experimental genetics
Mammary Neoplasms, Experimental pathology
Mice
Polychlorinated Dibenzodioxins administration & dosage
Pregnancy
Risk Factors
Dietary Fats adverse effects
Mammary Neoplasms, Experimental etiology
Polychlorinated Dibenzodioxins toxicity
Prenatal Exposure Delayed Effects etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1552-9924
- Volume :
- 118
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Environmental health perspectives
- Publication Type :
- Academic Journal
- Accession number :
- 20435547
- Full Text :
- https://doi.org/10.1289/ehp.0901047