Uppstad, H., Osnes, G. H., Cole, K. J., Phillips, D. H., Haugen, A., Mollerup, S. (2011) Sex differences in susceptibility to PAHs is an intrinsic property of human lung adenocarcinoma cells. LUNG CANCER, 71 (3). pp. 264-270. ISSN 0169-5002

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Abstract

Recent epidemiological studies have disputed whether females are at increased risk of lung cancer compared to males. However, several molecular studies are in support of an increased susceptibility to tobacco smoke carcinogens among females. Our earlier findings suggest that women display higher levels of smoking-induced bulky/hydrophobic DNA adducts which may be related to an increased expression of CYP1A1 in their lungs, compared to men. In this in vitro study, 11 lung adenocarcinoma cell lines, 6 of male and 5 of female origin, were exposed to benzo[a]pyrene, cigarette smoke condensate (CSC), or vehicle control. Subsequent expression analysis of genes in the polycyclic aromatic hydrocarbon bioactivation pathway was conducted with Real-Time RT-PCR. DNA adducts were measured in benzo[a]pyrene-exposed cells by P-32-postlabelling analysis, and CYP1 activity was measured by EROD assay. Analysis of benzo[a]pyrene-DNA adducts showed higher levels of adducts in cell lines from women compared to cell lines from men (p = 0.03). The results also revealed significant sex differences in CYP1A1 gene expression, both in untreated cells (p = 0.03), and in cells exposed to benzo[a]pyrene (p = 0.017) and cigarette smoke condensate (p = 0.0043). In CSC-exposed cells, significantly higher levels of CYP1 activity was found in cell lines of female origin (p = 0.049). These results are in support of the previously published in vivo data, providing evidence for a higher susceptibility to PAH of women's lungs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Item Type:	Article
Authors (ICR Faculty only):	Phillips, David
All Authors:	Uppstad, H., Osnes, G. H., Cole, K. J., Phillips, D. H., Haugen, A., Mollerup, S.
Additional Information:	ISI Document Delivery No.: 735LS Times Cited: 0 Cited Reference Count: 47 Uppstad, Heidi Osnes, Gro Helene Cole, Kathleen J. Phillips, David H. Haugen, Aage Mollerup, Steen The Norwegian Research Council ; The Norwegian Cancer Society ; Cancer Research UK The authors wish to thank Rita Baera, Ingrid Botnen and Unn W. Holm for excellent technical assistance. This study was supported by The Norwegian Research Council, The Norwegian Cancer Society, and Cancer Research UK. Elsevier ireland ltd Clare
Uncontrolled Keywords:	Benzo[a]pyrene Cigarette smoke condensate CYP1A1 CYP1B1 DNA adducts Sex differences Gene expression EROD assay estrogen-receptor-beta aryl-hydrocarbon receptor cancer patients dna-adducts ah-responsiveness histologic type expression women risk smoking
Research teams:	Closed research groups > Human Biomonitoring & Carcinogen Activation
Depositing User:	Barry Jenkins
Date Deposited:	05 Apr 2011 12:04
Last Modified:	09 Dec 2011 14:29
URI:	http://publications.icr.ac.uk/id/eprint/10613

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