Bioactivation of the proximal food mutagen 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP) to DNA-binding species by human mammary gland enzymes

Nutrition. 1998 Sep;14(9):683-6. doi: 10.1016/s0899-9007(98)00106-3.


We have investigated phase II activation of the food-derived mutagen 2-hydroxyamino-1-methyl-6-phenyl[4,5-b]pyridine (N-OH-PhIP) by cytosolic acetyltransferase, sulfotransferase, and tRNA synthetase/kinase 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 of 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 demonstrate that the human mammary gland has the capacity to metabolically activate a dietary mutagen by several enzyme systems, including acetyltransferase, sulfotransferase, tRNA synthetase/kinase, and prostaglandin hydroperoxidase catalysis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetyltransferases / metabolism
  • Adult
  • Amino Acyl-tRNA Synthetases / metabolism
  • Animals
  • Biotransformation
  • Cells, Cultured
  • DNA / metabolism*
  • DNA Adducts / metabolism
  • Enzyme Activation
  • Epithelial Cells / metabolism
  • Esterification
  • Female
  • Food*
  • Humans
  • Imidazoles / metabolism*
  • Mammary Glands, Animal / enzymology*
  • Middle Aged
  • Mutagens*
  • Pyridines / metabolism*
  • Sulfotransferases / metabolism


  • DNA Adducts
  • Imidazoles
  • Mutagens
  • Pyridines
  • 2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • DNA
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • Acetyltransferases
  • Sulfotransferases
  • Amino Acyl-tRNA Synthetases