Analysis of DNA and protein adducts of benzo[a]pyrene in human tissues using structure-specific methods.
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.
Boysen
Gunnar
G
University of Minnesota Cancer Center, Mayo Mail Code #806, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Hecht
Stephen S
SS
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis / Q000737:chemistry; D001564:Benzo(a)pyrene / Q000032:analysis* / Q000737:chemistry / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015394:Molecular Structure; D011506:Proteins / Q000032:analysis* / Q000737:chemistry / Q000187:drug effects
D002273:Carcinogens; D018736:DNA Adducts; D011506:Proteins; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA