Dietary Carcinogens and Breast Cancer

We have investigated phase II activation of the cooked meat mutagen 2-hydroxyamino-1-methyl-6-phenyl4,5-Bpyridine (N-OH-PhIP) by cytosolic acetyltransferase, sulfotransferase, and kinase enzymes from human breast tissue. Microsomal fractions of mammary epithelial cells were also examined for prostaglandin II synthetase activation of N-OH-PhIP. The results showed that all four enzymes can participate in activating N-OH-PhIP, thereby inducing PhIP-DNA adducts in human breast cells. However, not all individuals exhibited all four activities, instead each individual showed a combination of one or more activation pathways. Mammary tissue from rats activated N-OH-PhIP exclusively by acetyltransferase catalysis and therefore may not be a good model for food mutagen metabolism in humans. Alternatively, the breast cell lines MCF-7 and MCF-10A appeared to mimic metabolic mutagen processing of mammary tumor and normal cells, respectively. The dietary compound resveratrol inhibited PhIP-DNA adduct formation in primary cultures of human mammary epithelial cells and inhibited some phase II enzymes. The present findings provide the first demonstration that the human mammary gland has the capacity to metabolically activate a dietary mutagen by multiple enzyme systems. Furthermore, these studies indicate that resveratrol may have chemopreventive properties against human breast cancer.