Induction of NEIL1 and NEIL2 DNA glycosylases in aniline-induced splenic toxicity

Journal Article · Tue Feb 15 00:00:00 EST 2011 · Toxicology and Applied Pharmacology

OSTI ID:21535232

Huaxian, Ma; Jianling, Wang ^[1]; Abdel-Rahman, Sherif Z ^[2]; Hazra, Tapas K ^[3]; Boor, Paul J ^[1]

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1. Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States)
2. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555 (United States)
3. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

The mechanisms by which aniline exposure elicits splenotoxic response, especially the tumorigenic response, are not well-understood. Earlier, we have shown that aniline-induced oxidative stress is associated with increased oxidative DNA damage in rat spleen. The base excision repair (BER) pathway is the major mechanism for the repair of oxidative DNA base lesions, and we have shown an up-regulation of 8-oxoguanine glycosylase 1 (OGG1), a specific DNA glycosylase involved in the removal of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts, following aniline exposure. Nei-like DNA glycosylases (NEIL1/2) belong to a family of BER proteins that are distinct from other DNA glycosylases, including OGG1. However, contribution of NEIL1/2 in the repair of aniline-induced oxidative DNA damage in the spleen is not known. This study was, therefore, focused on evaluating if NEILs also contribute to the repair of oxidative DNA lesions in the spleen following aniline exposure. To achieve that, male SD rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. The BER activity of NEIL1/2 was assayed using a bubble structure substrate containing 5-OHU (preferred substrates for NEIL1 and NEIL2) and by quantitating the cleavage products. Aniline treatment led to a 1.25-fold increase in the NEIL1/2-associated BER activity in the nuclear extracts of spleen compared to the controls. Real-time PCR analysis for NEIL1 and NEIL2 mRNA expression in the spleen revealed 2.7- and 3.9-fold increases, respectively, in aniline-treated rats compared to controls. Likewise, Western blot analysis showed that protein expression of NEIL1 and NEIL2 in the nuclear extract of spleens from aniline-treated rats was 2.0- and 3.8-fold higher than controls, respectively. Aniline treatment also led to stronger immunoreactivity for NEIL1 and NEIL2 in the spleens, confined to the red pulp areas. These studies, thus, show that aniline-induced oxidative stress is associated with an induction of NEIL1/2. The increased NIEL-mediated BER activity is another indication of aniline-induced oxidative damage in the spleen and could constitute another important mechanism of removal of oxidative DNA lesions, especially in transcribed DNA following aniline insult.

• OSTI ID: 21535232
• Journal Information: Toxicology and Applied Pharmacology, Vol. 251, Issue 1; Other Information: DOI: 10.1016/j.taap.2010.12.001; PII: S0041-008X(10)00450-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANILINE
CONTROL
DAMAGE
DNA
DNA DAMAGES
DRINKING WATER
EXCISION REPAIR
MESSENGER-RNA
POLYMERASE CHAIN REACTION
PROTEINS
RATS
SPLEEN
TOXICITY
AMINES
ANIMALS
AROMATICS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
DNA REPAIR
GENE AMPLIFICATION
HYDROGEN COMPOUNDS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
REPAIR
RNA
RODENTS
VERTEBRATES
WATER