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

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.

Oxidative Cell Injury as a Predictor of Endometriosis Progression

“…9,10,21,25,[29][30][31][32][33] One of the important and sensitive indicators of DNA damage and a well-validated biomarker, resulting from oxidative stress, is the DNA guanine base oxidation product 8-OHdG, which was also studied in other publications. 9,19,21,34 The findings of our study are in concordance with Matsuzaki et al and Yamaguchi et al, who stated that patients with endometriosis have higher amounts of 8-OHdG-DNA damage compared to controls. Using high performance liquid chromatography electrochemical technique, Kao et al also showed higher levels of 8-OHdG in patients with endometriosis.…”

“…When the hydroxyl radicals reach the DNA they cause a base oxidation product 8-hydroxy-2-deoxyguanosine (8-OHdG) modifying the structural properties of DNA bases and thus damaging the DNA. [19][20][21] This marker has been used to estimate the progression of many diseases and in the promotion of carcinogens. 22,23 There are 3 types of defense against formation of ROS: (1) enzymatic inactivation: in order to access the first line of oxidative stress defense we evaluated the concentration of total antioxidant capacity (TAC).…”

Aristolochic acid suppresses DNA repair and triggers oxidative DNA damage in human kidney proximal tubular cells

“…These results suggest that the involvement of oxidative stress in AA-induced toxicity. 8-OHdG, one of the major abundant oxidative DNA damage markers which can efficiently repair by a glycosylase, OGG1 (62)(63)(64)(65). In this study, gene expression of OGG1 was decreased in cells exposed to AA.…”

Anilina. Dokumentacja dopuszczalnych wielkości narażenia zawodowego

“…Uszkodzone erytrocyty są wychwytywane głównie przez śledzionę, co może prowadzić nie tylko do uwolnienia aniliny i/lub jej metabolitów w tym narządzie, lecz także do nagromadzenia żelaza w wątrobie (hemosyderoza), co z kolei może powodować: peroksydację lipidów, utlenianie białek (Khan i in. 1997;1997a;1999;2003a;2003b;2003c) i DNA (Ma i in. 2008).…”