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Lobe-specific increases in malondialdehyde DNA adduct formation in the livers of mice following infection with Helicobacter hepaticus

Singh, Rajinder; Leuratti, Chiara; Josyula, Shylaja; Sipowicz, Marek A.; Diwan, Bhalchandra A.; Kasprzak, Kazimierz S.; Schut, Herman A.J.; Marnett, Lawrence J.; Anderson, Lucy M. and Shuker, David E.G. (2001). Lobe-specific increases in malondialdehyde DNA adduct formation in the livers of mice following infection with Helicobacter hepaticus. Carcinogenesis, 22(8) pp. 1281–1287.

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Helicobacter hepaticus infection is associated with chronic hepatitis and the development of liver tumours in mice. The underlying mechanism of this liver carcinogenesis is not clear but the oxidative stress associated with H. hepaticus infection may result in induction of lipid peroxidation and the generation of malondialdehyde. Malondialdehyde can react with deoxyguanosine in DNA resulting in the formation of the cyclic pyrimidopurinone N-1,N-2 malondialdehyde-deoxyguanosine (M(1)dG) adduct. This adduct has the potential to cause mutations that may ultimately lead to liver carcinogenesis. The objective of this study was to determine the control and infection-related levels of M(1)dG in the liver DNA of mice over time, using an immunoslot-blot procedure. The level of M(1)dG in control A/J mouse livers at 3, 6, 9 and 12 months averaged 37.5, 36.6, 24.8 and 30.1 adducts per 10(8) nucleotides, respectively. Higher levels of M(1)dG were detected in the liver DNA of H. hepaticus infected A/JCr mice, with levels averaging 40.7, 47.0, 42.5 and 52.5 adducts per 10(8) nucleotides at 3, 6, 9 and 12 months, respectively. There was a significant age dependent increase in the level of M(1)dG in the caudate and median lobes of the A/JCr mice relative to control mice. A lobe specific distribution of the M(1)dG adduct in both infected and control mice was noted, with the left lobe showing the lowest level of the adduct compared with the right and median lobes at all time points. In a separate series of mice experimentally infected with H. hepaticus, levels of 8-hydroxy-deoxyguanosine were significantly greater in the median compared with the left lobe at 12 weeks after treatment. In conclusion, these results suggest that M(1)dG occurs as a result of oxidative stress associated with H. hepaticus infection of mice, and may contribute to liver carcinogenesis in this model.

Item Type: Journal Article
ISSN: 1460-2180
Extra Information: Some of the symbols may not have transferred correctly into this bibliographic record and/or abstract.
Keywords: chronic active hepatitis; lipid-peroxidation products; A/JCR mice; bacterial pathogen; malonaldehyde; damage; tumors; tumours; pyrimidopurinone; mutagenicity; acids
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Item ID: 5781
Depositing User: David Shuker
Date Deposited: 09 Nov 2006
Last Modified: 14 Jan 2016 16:16
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