Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (85)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Randerath, E.
Right arrow Articles by Randerath, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Randerath, E.
Right arrow Articles by Randerath, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1988 Oxford University Press

research-article

Tissue distribution of covalent DNA damage in mice treated dermally with cigarette ‘tar’: preference for lung and heart DNA

Erika Randerath, Dinesh Mittal and Kurt Randerath

Department of Pharmacology, Baylor College of Medicine Houston, TX 77030, USA

The high incidence of lung cancer in smokers is thought to be related to the direct exposure of bronchial and pulmonary cells to carcinogens in inhaled cigarette smoke. Using a 32P-postlabeling assay for chemically induced covalent DNA alterations, we found that unfractionated, relatively non-polar cigarette smoke components bound preferentially to lung and heart DNA in female ICR mice. After 6 days of topical treatment with cigarette smoke condensate (CSC) equivalent to a total of 4.5 cigarettes, covalent DNA damage was estimated to be 6.2, 5.7, 3.9 and 1.9 times higher, respectively, in lung, heart, skin and kidney than in liver, ranging from approximately 1 adduct in 5.4 ± 0.7 x 106 DNA nucleotides in lung to 1 adduct in 3.3 ± 0.6 x 107 DNA nucleotides in liver. Spleen DNA was virtually adduct-free. Adducts occupied two extensive zones, designated diagonal radioactive zone (DRZ) 1 and DRZ 2, on TLC fingerprints. Preference for lung and heart DNA was also observed in mice treated for 1 or 3 days. An inverse association appeared to exist between the tissue distribution of CSC-induced covalent DNA damage and the reported activity of enzymes catalyzing the metabolism of xenobiotlcs (cytochrome P-450 monooxygenases, phase II enzymes) and toxic oxygen species (superoxide dismutase, catalase). The results suggest that the well-known pulmonary and cardiovascular organotropism of cigarette-smoking-associated adverse health effects may, in part, have its origin in the inherent capacity of cigarette smoke components to induce lesions in lung and heart DNA in a tissue-specific manner. Possible mechanisms and health implications of the preferential binding of presumably aromatic CSC constituents to lung and heart DNA are discussed.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Med. Genet.Home page
M C Cornelis, A El-Sohemy, and H Campos
Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction
J. Med. Genet., October 1, 2004; 41(10): 758 - 762.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
R. Thapliyal, S. S. Dolas, S. S. Pakhale, and G. B. Maru
Evaluation of DNA damage in mice topically exposed to total particulate matter from mainstream and sidestream smoke from cigarettes and bidis
Mutagenesis, September 1, 2004; 19(5): 413 - 421.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
F. J. Van schooten, A. Hirvonen, L. M. Maas, B. A. De mol, J. C. S. kleinjans, D. A. Bell, and J. D. Durrer
Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking, and aromatic DNA adduct levels in human right atrial tissue
FASEB J, October 1, 1998; 12(13): 1409 - 1417.
[Abstract] [Full Text]

Home page
 FASEB J.Home page
A. Izzotti, R. M. Balansky, P. M. Blagoeva, Z. I. Mircheva, L. Tulimiero, C. Cartiglia, and S. D. Flora
DNA alterations in rat organs after chronic exposure to cigarette smoke and/or ethanol ingestion
FASEB J, June 1, 1998; 12(9): 753 - 758.
[Abstract] [Full Text]

Home page
 Hum Exp ToxicolHome page
G. Scherer and E. Richter
Biomonitoring exposure to environmental tobacco smoke (ETS): A critical reappraisal
Human and Experimental Toxicology, August 1, 1997; 16(8): 449 - 459.
[Abstract] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.