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Lani · 08-28-2006, 12:56 PM

Study Reveals Smoking's Link to Breast Cancer [Reuters Health]
FRIDAY, Aug. 25 (HealthDay News) — Smoking causes normal breast cells to become cancerous by impairing their ability to repair their damaged DNA, U.S. researchers report.

In laboratory tests, researchers at the University of Florida (UF) exposed breast epithelial cells to cigarette smoke condensate — a tar gathered from a machine that that artificially "smokes" a cigarette.

When exposed to this tar — which contains all 4,000 chemicals found in cigarette smoke — the breast cells developed mutations characteristic of malignant cells.

DNA repair in the breast cells appears to be blocked when chemical components of the smoke activate a particular gene. This gene activity, in turn, interferes with an enzyme that plays a critical role in repairing damage to a cell's DNA, the study said.

If cells with damaged DNA survive long enough to divide and multiply, they can pass along their mutations to new cells, which can then become cancerous.

ABSTRACT: Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cells [Oncogene]
Our previous studies have shown that treatment with cigarette smoke condensate (CSC) transforms normal breast epithelial cell line, MCF-10A. In the present study, the mechanism of CSC-induced transformation of breast epithelial cells was examined. We first determined whether benzo[a]pyrene (B[a]P)- and CSC-induced levels of APC are capable of inhibiting long-patch base excision repair (LP-BER) since our earlier studies had shown that an interaction of APC with DNA polymerase ? (pol-?) blocks strand-displacement synthesis. With the use of a novel in vivo LP-BER assay, it was demonstrated that increased and decreased APC levels in different breast cancer cell lines were associated with a decrease or increase in LP-BER activity, respectively. The effect of APC on LP-BER in malignant and pre-malignant breast epithelial cell lines was produced by either overexpression or knockdown of APC. Furthermore, it was shown that the decreased LP-BER in B[a]P- or CSC-treated pre-malignant breast epithelial cells is associated with an increased level of APC and decreased cell growth. Our results suggest that the decreased growth allows cells to repair the damaged DNA before mitosis, and failure to repair damaged DNA has the potential to transform pre-malignant breast epithelial cells.

08-28-2006, 12:56 PM	#1
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	link between cigarette smoking and breast cancer identified Study Reveals Smoking's Link to Breast Cancer [Reuters Health] FRIDAY, Aug. 25 (HealthDay News) — Smoking causes normal breast cells to become cancerous by impairing their ability to repair their damaged DNA, U.S. researchers report. In laboratory tests, researchers at the University of Florida (UF) exposed breast epithelial cells to cigarette smoke condensate — a tar gathered from a machine that that artificially "smokes" a cigarette. When exposed to this tar — which contains all 4,000 chemicals found in cigarette smoke — the breast cells developed mutations characteristic of malignant cells. DNA repair in the breast cells appears to be blocked when chemical components of the smoke activate a particular gene. This gene activity, in turn, interferes with an enzyme that plays a critical role in repairing damage to a cell's DNA, the study said. If cells with damaged DNA survive long enough to divide and multiply, they can pass along their mutations to new cells, which can then become cancerous. ABSTRACT: Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cells [Oncogene] Our previous studies have shown that treatment with cigarette smoke condensate (CSC) transforms normal breast epithelial cell line, MCF-10A. In the present study, the mechanism of CSC-induced transformation of breast epithelial cells was examined. We first determined whether benzo[a]pyrene (B[a]P)- and CSC-induced levels of APC are capable of inhibiting long-patch base excision repair (LP-BER) since our earlier studies had shown that an interaction of APC with DNA polymerase ? (pol-?) blocks strand-displacement synthesis. With the use of a novel in vivo LP-BER assay, it was demonstrated that increased and decreased APC levels in different breast cancer cell lines were associated with a decrease or increase in LP-BER activity, respectively. The effect of APC on LP-BER in malignant and pre-malignant breast epithelial cell lines was produced by either overexpression or knockdown of APC. Furthermore, it was shown that the decreased LP-BER in B[a]P- or CSC-treated pre-malignant breast epithelial cells is associated with an increased level of APC and decreased cell growth. Our results suggest that the decreased growth allows cells to repair the damaged DNA before mitosis, and failure to repair damaged DNA has the potential to transform pre-malignant breast epithelial cells.