PCB News

BREAST CANCER: Cytochrome P4501B1 is induced by nonortho-substituted polychlorinated biphenyls

Clinical Oncology Week
February 17, 2003

"The effects of 12 nonortho-substituted polychlorinated biphenyl (PCB) congeners on the induction of human cytochrome P450 1B1 (CY1B1), an estradiol 4-hydroxylase, were investigated in MDA-MB-231 breast cancer cells," researchers in the United States report.

"Three independent quantitative assays were used, in which the rates of estrogen metabolism, the levels of the CYP1B1 and CYP1A1 mRNAs, and luciferase activities under the control of the CYP1B1 promoter were measured. Of the congeners investigated, 3,4,4',5-tetrachlorobiphenyl (PCB 81), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 3,4',5-trichlorobiphenyl (PCB 39) and 3,3',4,5-tetrachlorobiphenyl (PCB 78) were the most potent in each assay, causing 4-fold to 10-fold increases in response.

"Exposure to 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) resulted in elevated CYPI1B1 mRNA and increased CYP1B1-promoter driven luciferase activity, but caused depressed rather than elevated rates of E-2 metabolism due to inhibition of CYP1B1. The relative magnitudes of CYP1B1 induction by the PCB congeners, as determined by the three assays, were in close agreement, with the exception noted for PCB 169," wrote B.C. Spink and colleagues from New York State Department of Health.

The researchers concluded: "These results indicate that PCB structure-activity relationships for the induction of human CYP1B1 are similar to those observed for human CYP1A1, but differ somewhat from what has been reported for induction of rat CYP1A1."

Spink and colleagues published their study in Toxicology in Vitro (Induction of cytochrome P4501B1 in MDA-MB-231 human breast cancer cells by non-ortho-substituted polychlorinated biphenyls. Toxicol Vitro, 2002;16(6):695-704).

The contact person for this report is D.C. Spink, New York State Department Health, Wadsworth Center Laboratories & Research, Albany, NY 12201, USA.

To subscribe to the journal Toxicology in Vitro, contact the publisher: Pergamon-Elsevier Science Ltd., the Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK.

The information in this article comes under the major subject areas of Endocrinology, Toxicology, Gynecology, Oncology, Breast Cancer and Women's Health.

This article was prepared by Clinical Oncology Week editors from staff and other reports.