Dietary Carcinogens and Breast Cancer.
Annual rept. 1 Jul 96-30 Jun 97.
UNIVERSITY OF SOUTH ALABAMA MOBILE
Pagination or Media Count:
We have investigated phase II activation of the food-derived mutagen 2-hydroxyamino-1-methyl-6-phenyl4,5-Bpyridine N-OH-PhIP by cytosolic acetyltransferase, sulfotransferase, and tRNA synthetasekinase enzymes from human breast tissue. Cytosol from homogenates of mammary gland tissue obtained from breast reduction surgery or mastectomy was incubated with and without enzyme-specific cofactors, and mutagen binding to calf thymus DNA was quantified by 32P-postlabeling. In addition, microsomal fractions of mammary epithelial cells from some individuals were examined for prostaglandin H synthetase activation of N-OH-PhIP. Our results show that all four enzymes can participate in activating N-OH-PhIP, thus inducing PhIP-DNA adduct formation in human mammary cells. However, not all individuals exhibited all these activities instead each individual showed a combination of one or more activation pathways. The present findings provide the first demonstration that the human mammary gland has the capacity to metabolically activate a dietary mutagen by alternative enzyme systems, including acetyltransferase, sulfotransferase, tRNA synthetasekinase and prostaglandin hydroperoxidase catalysis.
- *BREAST CANCER
- CLINICAL MEDICINE
- DEOXYRIBONUCLEIC ACIDS
- HUMAN BODY
- INFECTIOUS DISEASES
- MEDICAL SERVICES
- RIBONUCLEIC ACIDS
- MAMMARY GLANDS
- PARTIAL BODY IRRADIATION
- Anatomy and Physiology
- Medicine and Medical Research
- Food, Food Service and Nutrition