Abstract 5303: Uptake and Efflux of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in human adipocytes

Abstract

Abstract Obesity has been linked to the development of numerous chronic diseases, including breast cancer. Although the association between obesity and breast cancer risk is clear in postmenopausal women, high body mass index (BMI) appears to protect against breast cancer in pre-menopausal women. The mechanistic basis of this “obesity paradox” is unknown. One hypothesis is that abundant adipose tissue in the mammary gland functions as a storage depot for lipid-soluble carcinogens of dietary origin, initially offering protection against exposures. Heterocyclic amines (HCAs) are pro-carcinogens that are formed from high-temperature cooked meats. Exposures to these compounds are ubiquitous in Western diets and 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP), the most mass-abundant HCA, is classified as a “probable human carcinogen.” To determine rates of influx of PhIP into adipocytes, differentiated Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes were treated with 5 µM plus 0.02 µCi 14C-PhIP for 0.5, 1, 2, 5, 10, 15, 30, 45, and 60 minutes, and media was removed at time points. Cells were re-suspended in scintillation fluid, and counted with a 1450 LSL & Luminescence Count (Perkin Elmer). Influx was rapid and PhIP continued to accumulate in the cells between 15 and 60 minutes. To determine efflux, SGBS cells were exposed to 5 µM plus 0.02 µCi 14C-PhIP and allowed to equilibrate for 30 minutes. Media was removed and the cells were washed with PBS. Radioactivity retained in SGBS cells was counted at 0.5, 1, 5, 10, 30, and 60 minutes. SGBS cells retained 50% of the radioactivity for more than 10 minutes, compared to other studies where PhIP efflux from pancreatic acinii and hepatocytes occurs within the first 15 seconds. Our data demonstrates that human adipocyte efflux is significantly slower than those in other type of cells reported in the literature, suggesting that human adipocytes can sequester PhIP, thereby protecting the breast from dietary exposure to carcinogens. Citation Format: Aiwei Yao-Borengasser, Lora J. Rogers, Susan A. Kadlubar. Uptake and Efflux of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in human adipocytes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5303. doi:10.1158/1538-7445.AM2014-5303