Elevation of 8-hydroxydeoxyguanosine in DNA from isolated mouse lung cells following in vivo treatment with aflatoxin B(1).
Aflatoxin B(1) (AFB(1)) is a mycotoxin produced by some strains of Aspergillus and is a recognized pulmonary and hepatic carcinogen. The most widely accepted mechanism of AFB(1) carcinogenicity involves bioactivation to AFB(1)-8,9-exo-epoxide and binding to DNA to form AFB(1)-N(7)-guanine. Another potential cause of DNA damage is AFB(1)-mediated stimulation of reactive oxygen species formation, leading to oxidation of DNA bases. The objective of this study was to determine the ability of AFB(1) to cause oxidative DNA damage in lung cell types of the A/J mouse. The formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) 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-OHdG formation occurred in both alveolar macrophage and Clara cell preparations isolated from A/J mice 2 h following treatment with a single tumorigenic dose of 50 mg/kg AFB(1) ip (n = 3, p < 0.05). Prior treatment with 300 kU/kg polyethylene glycol-conjugated catalase prevented the AFB(1)-induced increase in 8-OHdG 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 AFB(1) carcinogenicity.
Guindon
Katherine A
KA
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
Bedard
Leanne L
LL
Massey
Thomas E
TE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002469:Cell Separation; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004563:Electrochemistry; D005260:Female; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects
D009153:Mutagens; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D016604:Aflatoxin B1; D002374:Catalase; D003849:Deoxyguanosine