Accession Number : ADA360318
Title : Novel Cytochrome P45OlBl as a Mammary Cancer Risk Factor.
Descriptive Note : Final rept. 1Jul 94-30 Jun 98,
Corporate Author : WISCONSIN UNIV-MADISON
Personal Author(s) : Jefcoate, Colin R.
Report Date : JUL 1998
Pagination or Media Count : 230
Abstract : We have recently documented the expression of CYPIAl and CYP1B1, both of which are inducible by many environmental pollutants via the Ah receptor AhR, in human breast cells. The expression of CYP1B1 and CYP1Al has been quantitated in primary human breast luminal and basal epithelial cells LEC and BEC, respectively, in BF, and in estrogen receptor positive and negative (ER+ and ER-, respectively) breast tumor cell lines. CYP1B1 is constitutively expressed in LEC, BEC, and BF, whereas constitutive expression of CYPlAl is almost undetectable. Following 2,3,7,8- tetrachlorodibenzo(p)dioxin TCDD-induction, similar levels of CYPiBi and CYPlAl are expressed in LEC and BEC. Additionally, these cytochromes (CYPs) demonstrate widely different linkages to the estrogen receptor and to increased progression of tumorigenesis. We have shown that BF exhibit CYP1B1 activity and, most significantly, have shown that these cells also express functional ER. We have shown that CYP1B 1, indeed, mediates 4-hydroxylation in normal HBEC, but at low rates unless induced by environmental AhR agonists. The examination of PAH-DNA adduct formation in primary cultures of three donors has demonstrated substantial dose-dependent DNA adduct formation in the breast epithelia following exposure to dibenzo(a)pyrene, a prevalent environmental contaminant.
Descriptors : *MAMMARY GLANDS , *BREAST CANCER , ENVIRONMENTS , RISK , HUMANS , CONTAMINANTS , POLLUTANTS , INHIBITION , CELLS(BIOLOGY) , LOW RATE , SENSE ORGANS , BLOOD PROTEINS , ESTROGENS , DONORS(MEDICINE).
Subject Categories : MEDICINE AND MEDICAL RESEARCH
Distribution Statement : APPROVED FOR PUBLIC RELEASE