| First Author | Mulder JE | Year | 2014 |
| Journal | Toxicol Appl Pharmacol | Volume | 275 |
| Issue | 2 | Pages | 96-103 |
| PubMed ID | 24380836 | Mgi Jnum | J:211958 |
| Mgi Id | MGI:5577020 | Doi | 10.1016/j.taap.2013.12.016 |
| Citation | Mulder JE, et al. (2014) Up-regulation of nucleotide excision repair in mouse lung and liver following chronic exposure to aflatoxin B(1) and its dependence on p53 genotype. Toxicol Appl Pharmacol 275(2):96-103 |
| abstractText | Aflatoxin B(1)(AFB(1)) is biotransformed in vivo into an epoxide metabolite that forms DNA adducts that may induce cancer if not repaired. p53 is a tumor suppressor gene implicated in the regulation of global nucleotide excision repair (NER). Male heterozygous p53 knockout (B6.129-Trp53(tm1Brd)N5, Taconic) and wild-type mice were exposed to 0, 0.2 or 1.0 ppm AFB(1) for 26 weeks. NER activity was assessed with an in vitro assay, using AFB(1)-epoxide adducted plasmid DNA as a substrate. For wild-type mice, repair of AFB(1)-N7-Gua adducts was 124% and 96% greater in lung extracts from mice exposed to 0.2 ppm and 1.0 ppm AFB(1)respectively, and 224% greater in liver extracts from mice exposed to 0.2 ppm AFB(1)( p<0.05). In heterozygous p53 knockout mice, repair of AFB(1)-N7-Gua was only 45% greater in lung extracts from mice exposed to 0.2 ppm AFB(1) (p<0.05), and no effect was observed in lung extracts from mice treated with 1.0 ppm AFB(1)or in liver extracts from mice treated with either AFB(1)concentration. p53 genotype did not affect basal levels of repair. AFB(1)exposure did not alter repair of AFB(1)-derived formamidopyrimidine adducts in lung or liver extracts of either mouse genotype nor did it affect XPA or XPB protein levels. In summary, chronic exposure to AFB(1)increased NER activity in wild-type mice, and this response was diminished in heterozygous p53 knockout mice, indicating that loss of one allele of p53 limits the ability of NER to be up-regulated in response to DNA damage. |
