In Utero Exposure to Cadmium, Mammary Gland Development, and Breast Cancer Risk
Abstract
In utero exposures to estrogen or estrogen mimics such may alter later breast cancer risk. Some of these estrogen-responsive pathways utilized during fetal development, are re-employed at times of tissue remodeling or wound healing during adulthood. These signal transduction systems effect proliferation, differentiation and apoptosis which in turn may affect later breast cancer risk. The heavy metal cadmium potently binds to and activates the estrogen receptor, having a half life in the mammalian body of over 30 years. Previous studies have shown that in utero exposure to cadmium at the levels present in some human environments accelerated puberty onset and altered some of the indicators of mammary gland development in rats. In this study we sought to determine whether in utero exposure to low doses of dietary cadmium altered puberty-related body and mammary gland development and ultimately breast cancer risk. To test this possibility, we exposed pregnant rat dams to a diet similar to the human in fat content, 30% and very low doses of cadmium, 0.075 or 0.15 mg/kg feed cadmium throughout pregnancy. The effects on (i) birth weight, (ii) postnatal weight development, (iii) vaginal opening/puberty onset, (iv) mammary gland development, and (v) DMBA-induced mammary tumorigenesis were investigated. After parturition, all rats were switched to AIN93 laboratory chow. Birth-weight was not affected by fetal cadmium exposure, but the higher cadmium dose induced a long-lasting increase in postnatal body weight that was first detected on postnatal day 5 (p<0.04), and it accelerated vaginal opening (p<0.03). Final mammary tumor incidence was highest in the higher cadmium group (80% of rats developed tumors) and lowest in the lower cadmium group (56% tumor incidence) (p<0.001); 73% of the control rats developed mammary tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2007
- Accession Number
- ADA473699
Entities
People
- Jennifer D. Webster
Organizations
- Georgetown University