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ToxSci Advance Access published online on March 30, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm073
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Elevation of 8-hydroxydeoxyguanosine in DNA from Isolated Mouse Lung Cells following In Vivo Treatment with aflatoxin B1

Katherine A. Guindon1, Leanne L. Bedard1 and Thomas E. Massey1

1 Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada, K7L 3N6

To whom correspondence should be addressed: Dr. Thomas E. Massey, Professor and Head, Department of Pharmacology and Toxicology, Queen's University, Kingston, ON K7L 3N6, Canada, Phone: (613) 533-6115, Fax: (613) 533-6412, E-mail: masseyt{at}post.queensu.ca

Received December 21, 2006; revision received March 14, 2007; accepted March 22, 2007


  Abstract

Aflatoxin B1 is a mycotoxin produced by some strains of Aspergillus, and is a recognized pulmonary and hepatic carcinogen. The most widely accepted mechanism of aflatoxin B1 carcinogenicity involves bioactivation to aflatoxin B1- 8,9-exo-epoxide and binding to DNA to form aflatoxin B1-N7-Guanine. Another potential cause of DNA damage is aflatoxin B1-mediated stimulation of reactive oxygen species formation, leading to oxidation of DNA bases. The objective of this study was to determine the ability of aflatoxin B1 to cause oxidative DNA damage in lung cell types of the A/J mouse. The formation of 8-hydroxy-2'-deoxyguanosine in freshly isolated mouse lung alveolar macrophages, alveolar type II cells, and nonciliated bronchial epithelial (Clara) cells, was assessed by high performance liquid chromatography with electrochemical detection. An approximately 3 fold increase in 8-hydroxy-2'-deoxyguanosine formation occurred in both alveolar macrophage and Clara cell preparations isolated from A/J mice two hours following treatment with a single tumourigenic dose of 50 mg/kg aflatoxin B1 ip (n=3, P<0.05). Prior treatment with 300 kU/kg polyethylene glycol-conjugated catalase prevented the aflatoxin B1-induced increase in 8-hydroxy-2'-deoxyguanosine levels in all mouse lung cell preparations (n=3, P<0.05). These results support the possibility that oxidative DNA damage in mouse lung cells contributes to aflatoxin B1 carcinogenicity.

Key Words: Aflatoxin B1; mouse lung; 8-hydroxy-2'-deoxyguanosine; catalase.


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