Breast Cancer Research and Treatment 70: 47–54, 2001. © 2001 Kluwer Academic Publishers. Printed in the Netherlands. Report The expression of cytochrome P450 enzymes in human breast tumours and normal breast tissue Mumtaz Iscan 1 , Tuula Klaavuniemi 2 , Tulay Çoban 1 , Nilgun Kapucuo˘ glu 3 , Olavi Pelkonen 2 , and Hannu Raunio 2 1 Department of Toxicology, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey; 2 Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland; 3 Department of Pathology, Demetevler Oncology Hospital, Demetevler, Ankara, Turkey Key words: breast tumour, cytochrome P450, mRNA, normal breast tissue, reverse transcriptase-polymerase chain reaction Summary Environmental chemicals are one of the risk factors in breast cancer genesis. Cytochrome P450 (CYP) enzymes play a major role in the activation of these chemicals. Using highly specific and sensitive reverse transcriptase- polymerase chain reaction (RT-PCR) analysis, the expression profile of all major xenobiotic metabolizing CYP forms was screened in breast tumour and surrounding tumour free (control) breast tissue in a series of 20 sample pairs obtained from females with infiltrating ductal carcinoma. The levels of CYP1A1 mRNA were very low in both tumour and normal tissue. CYP1B1, CYP2B6, CYP2C, CYP2D6, CYP2E1, CYP4B1, and CYP11A1 expressions were positive in both tumours and control tissue. CYP2A6, CYP2A7, CYP2A13, CYP2F1, CYP3A4, CYP3A5, and CYP3A7 mRNAs were expressed neither in tumours nor in control tissue. These results show that several CYPs, responsible for the activation of a quite large number of procarcinogens and genotoxic estrogen metabolites, are expressed in breast tissue with a lack of qualitative differences in CYP expression at mRNA level between breast tumours and surrounding normal breast. Introduction Breast cancer is the most common cause of cancer related deaths in women. Although its etiology re- mains unknown, environmental, genetic, nutritional and hormonal factors are known to contribute to breast cancer risk [1]. A substantial proportion of breast can- cers have been proposed to be of environmental origin [2]. Numerous environmental chemicals are metabol- ized to mutagenic and/or carcinogenic metabolites by the cytochrome P450 (CYP) system, a multigene superfamily of enzymes that play a central role in activating and detoxifying a wide variety of xenobi- otics as well as endobiotics [3]. Of environmental factors, especially polycyclic aromatic hydrocarbons (PAHs) have been suggested to play a causative role in breast cancer etiology [1, 2]. Several PAHs are meta- bolized to mutagenic and/or carcinogenic metabolites by CYP1A1 [3, 4]. CYP1A1 is also essential in es- trogen metabolism, since it catalyzes the conversion of 17β-estradiol (E 2 ) to 2-hydroxy, 6α-hydroxy and 15α-hydroxy metabolites [5, 6]. CYP1A1 is induced by PAHs and xenoestrogens such as polychlorinated biphenyls (PCBs) which are stored in breast adipose tissue and may also play a role in breast cancer gen- esis [1, 7, 8]. The induction of CYP1A1 is under the control of the Ah (Aryl hydrocarbon) receptor [9]. CYP1B1, another PAH-responsive member of the CYP1 family, was identified recently [10, 11]. The hu- man CYP1B1 enzyme catalyses metabolic activation of structurally diverse environmental contaminants in- cluding PAHs and their dihydrodiol derivatives as well as arylamines and heterocyclic amines [12]. CYP1B1 also catalyses the conversion of E 2 to the mutagenic 4-hydroxyestradiol (4- OHE 2 ) [13, 14].