Effects of maternal dietary exposure to cadmium during pregnancy on mammary cancer risk among female offspring

Posted by Article Type, Issue, Original Article, Vol 12, Issue 1Posted on

Jennifer Davis1, Galam Khan2, Mary Beth Martin2, Leena Hilakivi-Clarke3
1Department of Oncology, Lombardi Comprehensive Cancer Center; Tumor Biology Graduate Program, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057, USA.
2Department of Oncology, Lombardi Comprehensive Cancer Center, Washington, DC 20057, USA.
3Department of Oncology, Lombardi Comprehensive Cancer Center; Department of Oncology, Georgetown University, Research Building, Room E407, 3970 Reservoir Road, NW, Washington DC 20057, USA.
DOI: 10.4103/1477-3163.114219

ABSTRACT

Background: Since heavy metal cadmium is an endocrine disrupting chemical, we investigated whether maternal exposure to cadmium during the pregnancy alters mammary tumorigenesis among female offspring. Methods: From gestation day 10 to day 19, pregnant rat dams were fed modified American Institute of Nutrition (AIN93G) diet containing 39% energy from fat (baseline diet), or the baseline diet containing moderate (75 μg/kg of feed) or high (150 μg/kg) cadmium levels. Some dams were injected with 10 μg 17β-estradiol (E2) daily between gestation days 10 and 19. Results: Rats exposed to a moderate cadmium dose in utero were heavier and exhibited accelerated puberty onset. Both moderate and high cadmium dose led to increased circulating testosterone levels and reduced the expression of androgen receptor in the mammary gland. The moderate cadmium dose mimicked the effects of in utero E2 exposure on mammary gland morphology and increased both the number of terminal end buds and pre-malignant hyperplastic alveolar nodules (HANs), but in contrast to the E2, it did not increase 7, 12-dimethylbenz (a) anthracene-induced mammary tumorigenesis. Conclusions: The effects of in utero cadmium exposure were dependent on the dose given to pregnant dams: Moderate, but not high, cadmium dose mimicked some of the effects seen in the in utero E2 exposed rats, such as increased HANs in the mammary gland.

Keywords: Androgen receptor, cadmium, estradiol, estrogen receptor, in utero exposure, mammary cancer, maternal diet, testosterone