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Analysis of DNA and protein adducts of benzo[a]pyrene in human tissues using structure-specific methods
Gunnar Boysen1, Stephen S Hecht
1University of Minnesota Cancer Center, Mayo Mail Code #806, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Abstract:
We review studies which investigate the presence, using structure-specific analytical methods, of DNA or protein adducts of the carcinogen benzo[a]pyrene (BaP) in human tissues. The analytical methods include high performance liquid chromatography with fluorescence detection and gas chromatography-mass spectrometry. Although, for DNA detection these methods are somewhat less sensitive than non-specific techniques such as 32P-postlabeling and immunoassay, they have the distinct advantage of providing reliable structural information. In order to achieve adequate sensitivity, these methods often require the use of fairly large amounts of DNA (>100 microg) or protein (50-100mg). Most studies reviewed here measured tetraols released from DNA or protein by hydrolysis of adducts derived from (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), a major ultimate carcinogen of BaP. BPDE-DNA adducts were detected in 39% of 705 samples analyzed. BPDE-protein adducts were found in 59% of 772 samples. There was no single exposure situation that led to an overwhelming presence of detectable adducts. For example, BPDE-DNA adducts were detected in 45% of smokers, 33% of former smokers, 52% of non-smokers, 39% of occupationally exposed individuals, and 34% of environmentally exposed people. Adduct levels were influenced by polymorphisms in carcinogen metabolizing genes such as GSTM1, the presence of which was frequently protective. The relatively high occurrence of non-detectable adducts may result from low levels of BaP exposure and host factors such as genetic polymorphisms. Our analysis demonstrates that the presence of BaP adducts in human tissues cannot be assumed, even in situations where exposure to BaP is relatively high.
Insights
This review found that benzo[a]pyrene (BaP) DNA and protein adducts are present in human tissues, but their detection is not guaranteed, even with high exposure. Genetic factors influence adduct presence.
Area of Science:
- Environmental Health Sciences
- Molecular Toxicology
- Biomarker Research
Background:
- Benzo[a]pyrene (BaP) is a ubiquitous environmental carcinogen.
- BaP exposure can lead to the formation of DNA and protein adducts, which are indicators of exposure and potential carcinogenicity.
- Accurate detection of these adducts in human tissues is crucial for understanding exposure and health risks.
Purpose of the Study:
- To review studies investigating the presence of benzo[a]pyrene (BaP) DNA and protein adducts in human tissues.
- To evaluate the effectiveness and limitations of structure-specific analytical methods for adduct detection.
- To analyze factors influencing adduct occurrence, including exposure levels and genetic polymorphisms.
Main Methods:
- Review of studies employing structure-specific analytical methods like high-performance liquid chromatography with fluorescence detection and gas chromatography-mass spectrometry.
- Analysis of adducts derived from (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), a major BaP metabolite.
- Examination of data on BPDE-DNA and BPDE-protein adduct detection rates across various exposure groups.
Main Results:
- BPDE-DNA adducts were detected in 39% of samples, and BPDE-protein adducts in 59% of samples.
- Adduct detection varied across exposure groups (smokers, non-smokers, occupational, environmental) and was not consistently high.
- Genetic polymorphisms, such as in GSTM1, influenced adduct levels, often showing a protective effect.
Conclusions:
- The presence of BaP adducts in human tissues is not ubiquitous and cannot be assumed, even with significant exposure.
- Low exposure levels and host genetic factors contribute to the frequent occurrence of non-detectable adducts.
- Structure-specific analytical methods provide reliable structural information but may require substantial sample amounts for adequate sensitivity.
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