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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
Acute benzo[a]pyrene treatment causes different antioxidant response and DNA damage in liver, lung, brain, stomach
Chun Deng1, Fan Dang1, Jianghong Gao2
1Department of Biological Science and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710049, China.
Abstract:
Acute effects of oxidative damage induced by benzo[a]pyrene (B[a]P) on various organs are still not clear. In this study, we investigated oxidative stress and DNA damage in liver, lung, stomach, brain and kidney of ICR male mice induced by acute B[a]P treatment. B[a]P treatment led to a significant decrease at the different doses in body weight. For the variations of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione (GSH) and GSH/GSSG, significant increases were observed at 24 h, then decreased till 72 h after B[a]P injection. The increase percent indicated in a dose- dependent decrease manner. However, glutathione peroxidase (GPx), GSSG and MDA were significantly increased in a time- and dose-dependent increase manner. DNA damage showed the significant and top levels at 24 h, and increased in proportion to the doses of B[a]P treatment. The total induction could be indicated by the variation of MDA at 24 h after B[a]P injection and showed the following order of predominance: lung > liver > kidney = stomach > brain. This was further certificated by histopathological changes in the examined organs. Additionally, the levels of serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), and blood urea nitrogen (UN), creatinine were also significantly increased at 24 h after B[a]P injection. These findings suggested the disturbance of antioxidant responses and aggravation of DNA damages, and the different responses on various organs induced by acute B[a]P treatment in organism.
Insights
Acute benzo[a]pyrene (B[a]P) exposure causes oxidative stress and DNA damage in mice organs. The lung and liver showed the most significant damage, indicating B[a]P
Area of Science:
- Toxicology
- Environmental Health
- Biochemistry
Background:
- Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon found in environmental pollutants.
- The acute effects of B[a]P on oxidative stress and DNA damage across multiple organs are not fully understood.
- Understanding these effects is crucial for assessing B[a]P's health risks.
Purpose of the Study:
- To investigate the acute effects of B[a]P on oxidative stress and DNA damage in the liver, lung, stomach, brain, and kidney of ICR male mice.
- To determine the time- and dose-dependent responses of antioxidant enzymes and oxidative stress markers.
- To correlate biochemical findings with histopathological changes.
Main Methods:
- Mice were administered varying doses of B[a]P acutely.
- Body weight, antioxidant enzyme levels (SOD, CAT, GST, GPx), glutathione levels (GSH, GSSG), lipid peroxidation marker (MDA), and DNA damage were measured at 24 and 72 hours post-injection.
- Serum markers of organ damage (GOT, GPT, BUN, creatinine) were analyzed.
- Histopathological examination of organs was performed.
Main Results:
- B[a]P treatment significantly decreased body weight.
- Antioxidant enzymes showed complex time- and dose-dependent changes, with initial increases followed by decreases.
- Markers of oxidative stress (MDA, GSSG) and DNA damage increased significantly in a time- and dose-dependent manner.
- Organ damage predominance followed the order: lung > liver > kidney = stomach > brain, confirmed by histopathology.
- Serum GOT, GPT, BUN, and creatinine levels were elevated.
Conclusions:
- Acute B[a]P exposure disrupts antioxidant responses and exacerbates DNA damage in mice.
- Different organs exhibit varying sensitivities to B[a]P-induced toxicity.
- The lung and liver are particularly vulnerable to acute B[a]P insult.
- Findings highlight the significant toxic potential of B[a]P even after acute exposure.
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