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Published ahead of print on April 5, 2007, doi:10.1164/rccm.200611-1655PP

Am. J. Respir. Crit. Care Med., Volume 176, Number 2, July 2007, 113-120

A more recent version of this article appeared on July 15, 2007
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Submitted on November 18, 2006
Accepted on April 4, 2007

COPD and Lung Cancer in Women: Examining Sex Differences in Cigarette Smoke Metabolism

Sigal Ben-Zaken Cohen1, Peter D Pare2, S.F. Paul Man2, and Don D Sin2*

1 The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research (St. Paul's Hospital), Vancouver, BC, Canada, 2 The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research (St. Paul's Hospital), Vancouver, BC, Canada; Department of Medicine (Division of Respirology), The University of British Columbia, Vancouver, BC, Canada

* To whom correspondence should be addressed. E-mail: dsin{at}mrl.ubc.ca.

Smoking-related lung diseases such as chronic obstructive pulmonary disease (COPD)and lung cancer are growing epidemics in women in the United States and elsewhere. Although some of this disturbing trend in women can be attributed to changing smoking habits, there is emerging evidence that women may be biologically more susceptible to the harmful effects of cigarette smoke than are men. Estrogen and related compounds may up-regulate the expression of cytochrome P450 (CYP) enzymes in lungs and liver, which are involved in the metabolism of various constituents of cigarette smoke. Although metabolism of foreign substances is usually beneficial in eliminating potential toxins from the body, in some instances, the metabolic process can transform harmless substances into toxic chemicals through a process called metabolic bioactivation. One important xenobiotic substrate for CYPs in cigarette smoke is polycyclic aromatic hydrocarbon, which in its native form is relatively harmless in small doses but upon bioactivation by CYP enzymes, can become very toxic substances for the lungs. In this paper, we explore CYP and other related pathways as potential mechanisms and targets of future research and novel discoveries to curb the growing epidemic of COPD and lung cancer in women.
Key words: gender, sex, cytochrome p450, COPD, lung cancer




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