title: The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines.
abstract: Tamoxifen is utilized in breast cancer therapy and in chemoprevention. Tamoxifen may enhance risk for other neoplasias, especially endometrial cancer. The risk:benefit depends on the rate of metabolic activation versus detoxication. Cytochrome P450-dependent alpha-hydroxylation, followed by sulfonation, represents a metabolic activation pathway, producing products capable of covalent DNA adduction. In contrast, tamoxifen N-oxygenation represents a detoxication pathway, with the caveat that N-oxides can be reduced back to the parent amines. The N-oxygenation pathway will be the focus for this review. Dr. David Kupfer pioneered studies on cytochrome P450 and flavin-containing monooxygenase (FMO) tamoxifen metabolism. We collaborated with Dr. Kupfer's laboratory and recently determined that the low level of tamoxifen N-oxide production in human liver microsomes may be explained by the kinetics of FMO1 versus FMO3.
authors: Department of Environmental and Molecular Toxicology, The Linus Pauling Institute, Oregon State University, Corvallis, 97331, USA.
authors: Sharon K
authors: SK
authors: Krueger
authors: Jonathan E
authors: JE
authors: Vandyke
authors: David E
authors: DE
authors: Williams
authors: Ronald N
authors: RN
authors: Hines