Table 1

Substrates of human carcinogen-metabolizing enzymes expressed in the human mammary gland

EnzymeDetected asSubstrate(s) implicated in breast carcinogenesisa
CYP1A1 (54)mRNA levels, immunoreactive protein and enzyme activityDMBA (54) and other PAHs (80) activated by dihydrodiol epoxide formation
CYP1A1 (58)mRNA levelsIQ (58) activated via N-hydroxylation
CYP1B1 (54)mRNA levels, immunoreactive protein and enzyme activityDMBA (54) activated by dihydrodiol epoxide formation
CYP1B1 (58)mRNA levelsIQ (58) activated via N-hydroxylation
CYP1B117β-estradiol (83) activated by 4-hydroxylation (also see review of estrogens and cancer, ref. 5 ) PAHs activated by dihydriol epoxide formation (80)
CYP2C (78)Immunoreactive protein17β-estradiol (101) activated by C2-hydroxylation
CYP2D6 (68, 70)mRNA levels and immunoreactive proteinNNK activated by C-hydroxylation (182)
CYP2E1 (68)immunoreactive proteinN-nitrosodialkylamines activated (183)
CYP3A4/5 (70)mRNA levelsMeIQ activated by N-hydroxylation (109), aflatoxin B1 activated (110)
Catechol-O-methyltransferase (115)Enzyme activityCatechol estrogens (120) detoxified by O-methylation
Epoxide hydrolase (77)Immunoreactive proteinPAHs (184) activated by epoxide hydrolysis
N-Acetyltransferase (NAT1) (56)mRNA and enzyme activityN-OH-IQ and N-OH-PhIP (56) activated by O-acetylation
N-Acetyltransferase (NAT1) (69)mRNA levels, immunoreactive protein, and enzyme activity levelsN-OH-IQ (69) activated by O-acetylation
AAs detoxified by N-acetylation (reviewed in Ref. 125 )
(Estrogen) sulfotransferase (142)Immunoreactive protein and enzyme activityN-OH-IQ (71) activated by O-sulfation
HAs detoxified by N-sulfation (185)
Sulfatase (77)Enzyme activityNA
Enzyme activityHAs (185) detoxified by N-glucuronidation
UDP-glucuronyltransferase (77)
Glucuronidase (77)Enzyme activityNA
Glutathione-S-transferase (78)Immunoreactive protein and enzyme activityN-OH-PhIP (154) detoxified by glutathione conjugation
Lactoperoxidaseb (160)mRNA levelsNA
12-Lipoxygenase (178)mRNA levelsAflatoxin B1 activated by epoxidation (186)
4-Aminobiphenyl activated by oxidation (187)
  • a Only published information on human enzymes is included; NA, information not available. Substrate abbreviations: DMBA, 7-12-dimethylbenz[a]anthracene (a polycyclic aromatic hydrocarbon); HAs, heterocyclic amines; IQ, 2-amino-3-methylimidazo[4,5-f]quinoline (heterocyclic amine); MeIQ, 2-amino-3,4-dimethylimidazo[4,5-f] quinoline (heterocyclic amine); MeIQx, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (heterocyclic amine); N-OH-IQ, N-hydroxy-IQ; N-OH-PhIP, N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (tobacco nitrosamine); PAHs, polycyclic aromatic hydrocarbons.

  • b Substrate specificity for the human enzyme is unknown.