In situ hybridization and immunohistochemical analysis of cytochrome P4501B1 expression in human normal tissues

Cytochrome P450 1B1 (CYP1B1) is a recently cloned dioxin-inducible form of the cytochrome P450 supergene family of xenobiotic-metabolizing enzymes. CY P1B1 is constitutively expressed mainly in extrahepatic tissues and is indu cible by aryl hydrocarbon receptor ligands. Human CYP1B1 is involved in act ivation of chemically diverse human procarcinogens, including polycyclic ar omatic hydrocarbons and some aromatic amines, as well as the endogenous hor mone 17 beta -estradiol. The metabolism of 17 beta -estradiol by CYP1B1 for ms 4-hydroxyestradiol, a product believed to be important in estrogen-induc ed carcinogenesis. Although the distribution of CYP1B1 mRNA and protein in a number of human normal tissues has been well documented, neither the cell s expressing CYP1B1 in individual tissue nor the intracellular localization of the enzyme has been thoroughly characterized. In this study, using nonr adioactive in situ hybridization and immunohistochemistry, we examined the cellular localization of CYP1B1 mRNA and protein in a range of human normal tissues. CYP1B1 mRNA and protein were expressed in most samples of parench ymal and stromal tissue from brain, kidney, prostate, breast, cervix, uteru s, ovary, and lymph nodes. In most tissues, CYP1B1 immunostaining was nucle ar. However, in tubule cells of kidney and secretory cells of mammary gland , immunoreactivity for CYP1B1 protein was found in both nucleus and cytopla sm. This study demonstrates for the first time the nuclear localization of CYP1B1 protein. Moreover, the constitutive expression and wide distribution of CYP1B1 mRNA and protein in many human normal tissues suggest functional roles for CYP1B1 in the bioactivation of xenobiotic procarcinogens and end ogenous substrates such as estrogens.