EXPRESSION OF CYTOCHROMES P450 IN HUMAN BREAST-TISSUE AND TUMORS

In an effort to determine which members of the cytochrome P450 (CYP) s uperfamily are expressed in human breast tissue and tumors, RNA-polyme rase chain reaction studies have been undertaken, Detection of express ed CYP mRNAs identifies those forms of the enzyme that are capable of expression in breast tissue, and provides insight into the potential f or in situ xenobiotic and therapeutic drug metabolism, CYP1A1 mRNA was present in (5/11) breast tissues and (6/13) tumors, When normal and t umor tissues were from the same individuals, higher amplification occu rred in normal tissues. CYP1B1 mRNA was present in all but one tissue, and CYP2C mRNA forms were present in all of the tissues. CYP3A4 mRNA was present in (8/11) normal breast tissues and (2/13) tumor tissues, and CYP3A5 mRNA was present in (9/11) normal tissues and (2/13) tumor tissues, The expression of the CYP3A mRNA forms was not coincident, su ggesting differential regulation. CYP2D6 mRNA was present in (10/11) n ormal breast tissue and (10/13) tumors, Two splice variants of CYP2D6 mRNA were also detected; one with a 207 bp intron spliced in was detec ted in all of the normal tissue samples and (11/13) tumors, whereas an other (which lacks a 3'-portion of exon 6) was detected in (9/11) norm al breast tissues and (7/13) tumors, Thus, examples of each of the xen obiotic-metabolizing CYP1, CYP2, and CYP3 subfamilies were detected in low levels in human normal breast tissue and tumors. The machinery fo r possible in site bioactivation of xenobiotics and modification of th erapeutic drugs is thus present in human breast tissue.