| Title |
The impact of p53 on DNA damage and metabolic activation of the environmental carcinogen benzo[a]pyrene: effects in Trp53(+/+), Trp53(+/–) and Trp53(−/−) mice
|
|---|---|
| Published in |
Archives of Toxicology, May 2015
|
| DOI | 10.1007/s00204-015-1531-8 |
| Pubmed ID | |
| Authors |
Annette M. Krais, Ewoud N. Speksnijder, Joost P. M. Melis, Radek Indra, Michaela Moserova, Roger W. Godschalk, Frederik-J. van Schooten, Albrecht Seidel, Klaus Kopka, Heinz H. Schmeiser, Marie Stiborova, David H. Phillips, Mirjam Luijten, Volker M. Arlt |
| Abstract |
The tumour suppressor p53 is one of the most important cancer genes. Previous findings have shown that p53 expression can influence DNA adduct formation of the environmental carcinogen benzo[a]pyrene (BaP) in human cells, indicating a role for p53 in the cytochrome P450 (CYP) 1A1-mediated biotransformation of BaP in vitro. We investigated the potential role of p53 in xenobiotic metabolism in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with BaP. BaP-DNA adduct levels, as measured by (32)P-postlabelling analysis, were significantly higher in liver and kidney of Trp53(-/-) mice than of Trp53(+/+) mice. Complementarily, significantly higher amounts of BaP metabolites were also formed ex vivo in hepatic microsomes from BaP-pretreated Trp53(-/-) mice. Bypass of the need for metabolic activation by treating mice with BaP-7,8-dihydrodiol-9,10-epoxide resulted in similar adduct levels in liver and kidney in all mouse lines, confirming that the influence of p53 is on the biotransformation of the parent compound. Higher BaP-DNA adduct levels in the livers of Trp53(-/-) mice correlated with higher CYP1A protein levels and increased CYP1A enzyme activity in these animals. Our study demonstrates a role for p53 in the metabolism of BaP in vivo, confirming previous in vitro results on a novel role for p53 in CYP1A1-mediated BaP metabolism. However, our results also suggest that the mechanisms involved in the altered expression and activity of the CYP1A1 enzyme by p53 in vitro and in vivo are different. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Mexico | 1 | 50% |
| Netherlands | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 30 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 5 | 17% |
| Student > Ph. D. Student | 4 | 13% |
| Student > Master | 4 | 13% |
| Researcher | 2 | 7% |
| Professor > Associate Professor | 2 | 7% |
| Other | 5 | 17% |
| Unknown | 8 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 20% |
| Environmental Science | 5 | 17% |
| Chemistry | 3 | 10% |
| Agricultural and Biological Sciences | 3 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 2 | 7% |
| Unknown | 10 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 May 2015.
All research outputs
#18,942,832
of 24,143,470 outputs
Outputs from Archives of Toxicology
#2,244
of 2,736 outputs
Outputs of similar age
#184,653
of 270,657 outputs
Outputs of similar age from Archives of Toxicology
#25
of 34 outputs
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