Oxidative DNA damage and its repair in rat spleen following subchronic exposure to aniline

Huaxian Ma, Jianling Wang, Sherif Abdel-Rahman, Paul J. Boor, M Khan

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The mechanisms by which aniline exposure elicits splenotoxic response, especially the tumorigenic response, are not well-understood. Splenotoxicity of aniline is associated with iron overload and generation of reactive oxygen species (ROS) which can cause oxidative damage to DNA, proteins and lipids (oxidative stress). 8-Hydroxy-2′-deoxyguanosine (8-OHdG) is one of the most abundant oxidative DNA lesions resulting from ROS, and 8-oxoguanine glycosylase 1 (OGG1), a specific DNA glycosylase/lyase enzyme, plays a key role in the removal of 8-OHdG adducts. This study focused on examining DNA damage (8-OHdG) and repair (OGG1) in the spleen in an experimental condition preceding a tumorigenic response. To achieve that, male Sprague-Dawley rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. Aniline treatment led to a significant increase in splenic oxidative DNA damage, manifested as a 2.8-fold increase in 8-OHdG levels. DNA repair activity, measured as OGG1 base excision repair (BER) activity, increased by ∼ 1.3 fold in the nuclear protein extracts (NE) and ∼ 1.2 fold in the mitochondrial protein extracts (ME) of spleens from aniline-treated rats as compared to the controls. Real-time PCR analysis for OGG1 mRNA expression in the spleen revealed a 2-fold increase in expression in aniline-treated rats than the controls. Likewise, OGG1 protein expression in the NEs of spleens from aniline-treated rats was ∼ 1.5 fold higher, whereas in the MEs it was ∼ 1.3 fold higher than the controls. Aniline treatment also led to stronger immunostaining for both 8-OHdG and OGG1 in the spleens, confined to the red pulp areas. It is thus evident from our studies that aniline-induced oxidative stress is associated with increased oxidative DNA damage. The BER pathway was also activated, but not enough to prevent the accumulation of oxidative DNA damage (8-OHdG). Accumulation of mutagenic oxidative DNA lesions in the spleen following exposure to aniline could play a critical role in the tumorigenic process.

Original languageEnglish (US)
Pages (from-to)247-253
Number of pages7
JournalToxicology and Applied Pharmacology
Volume233
Issue number2
DOIs
StatePublished - Dec 1 2008

Fingerprint

DNA Damage
Rats
Repair
Spleen
DNA
DNA Repair
Oxidative stress
Drinking Water
Reactive Oxygen Species
Oxidative Stress
aniline
DNA Glycosylases
Lyases
Iron Overload
Mitochondrial Proteins
Nuclear Proteins
Pulp
Sprague Dawley Rats
8-hydroxyguanine
Real-Time Polymerase Chain Reaction

Keywords

  • 8-OHdG
  • Aniline
  • Base excision repair
  • DNA damage
  • Immunochemical localization
  • OGG1
  • Reactive oxygen species
  • Spleen

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Oxidative DNA damage and its repair in rat spleen following subchronic exposure to aniline. / Ma, Huaxian; Wang, Jianling; Abdel-Rahman, Sherif; Boor, Paul J.; Khan, M.

In: Toxicology and Applied Pharmacology, Vol. 233, No. 2, 01.12.2008, p. 247-253.

Research output: Contribution to journalArticle

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