p53-dependent Global genomic repair of benzo[a]pyrene-7,8-diol-9,10-epoxide adducts in human cells

The global genomic repair of DNA adducts formed by the human carcinogen (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) has been studied by 32P-postlabeling in human fibroblasts in which p53 expression can be regulated. At low BPDE adduct levels (10-50 adducts/10(8) nucleotides), repair was r...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-02, Vol.60 (3), p.517-521
Main Authors: LLOYD, D. R, HANAWALT, P. C
Format: Article
Language:English
Subjects:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - analysis
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Cells, Cultured
Chemical agents
DNA Adducts - analysis
DNA Repair
Humans
Medical sciences
Tetracycline - pharmacology
Tumor Suppressor Protein p53 - analysis
Tumor Suppressor Protein p53 - physiology
Tumors
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Summary:The global genomic repair of DNA adducts formed by the human carcinogen (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) has been studied by 32P-postlabeling in human fibroblasts in which p53 expression can be regulated. At low BPDE adduct levels (10-50 adducts/10(8) nucleotides), repair was rapid and essentially complete within 24 h in p53+ cells, whereas no repair was detected within 72 h in similarly treated p53- cells. At 10-fold higher BPDE adduct levels, repair under both conditions was rapid up to 8 h, after which a low level of adducts persisted only in p53- cells. These results demonstrate a dependence on p53 for the efficient repair of BPDE adducts at levels that are relevant to human environmental exposure and, thus, have significant implications for human carcinogenesis.
ISSN:0008-5472
1538-7445