Metabolic biotransformation of estradiol in human mammary explant cultures.
The metabolism of E2 via the 16 alpha-hydroxylation pathway is reported to be elevated in breast cancer patients as well as in subjects at high risk for developing breast cancer. The biological relevance of the metabolic pathway during the initiational events that lead to the tumorigenic transformation of mammary epithelium is not fully understood. The results obtained from the in vitro experiments discussed in this report permit the following conclusions: 1. Human mammary TDLU, the presumptive target site for breast cancer, possesses metabolic competence to biotransform E2. 2. The biotransformation of E2 in TDLU via the 16 alpha-hydroxylation pathway is responsive to endogenous hormonal changes and to the presence of cancer, and is susceptible to carcinogenic insult. 3. The relative extent of E2 16 alpha-hydroxylation may constitute a sensitive metabolic marker for evaluating the susceptibility of noninvolved mammary epithelium to carcinogen-induced transformation.
Telang
N T
NT
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Axelrod
D M
DM
Bradlow
H L
HL
Osborne
M P
MP
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001564:Benzo(a)pyrene / Q000633:toxicity; D014408:Biomarkers, Tumor / Q000032:analysis; D001940:Breast / Q000187:drug effects / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D003043:Cocarcinogenesis; D046508:Culture Techniques; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000009:adverse effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology; D008875:Middle Aged; D039181:Steroid 16-alpha-Hydroxylase
D014408:Biomarkers, Tumor; D001564:Benzo(a)pyrene; D004958:Estradiol; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D039181:Steroid 16-alpha-Hydroxylase