Detection and Quantification of Depurinated Benzo[<i>a</i>]pyrene-Adducted DNA Bases in the Urine of Cigarette Smokers and Women Exposed to Household Coal Smoke

Casale, George P.; Singhal, Maria; Bhattacharya, Sumitra; RamaNathan, Regulan; Roberts, Kenneth P.; Barbacci, Damon C.; Zhao, Jun; Jankowiak, Ryszard; Gross, Michael L.; Cavalieri, Ercole L.; Small, Gerald J.; Rennard, Stephen I.; Mumford, Judy L.; Shen, Meilan

doi:10.1021/tx000012y

Cited by 66 publications

(49 citation statements)

References 39 publications

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“…The diol epoxide pathway is not the only mechanism for adduct formation from PAH. Depurinating adducts have been detected as a result of one electron oxidation, and adducts resulting from quinone formation have also been characterized (Casale et al, 2001;Penning et al, 1999). Adducts are also formed via 9-hydroxy-BaP-4,5-oxide (Ross and Nesnow, 1999).…”

Section: Adduct Structuresmentioning

confidence: 99%

Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers

et al. 2002

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It is estimated that cigarette smoking kills over 1 000 000 people each year by causing lung cancer as well as many other neoplasmas. p53 mutations are frequent in tobaccorelated cancers and the mutation load is often higher in cancers from smokers than from nonsmokers. In lung cancers, the p53 mutational patterns are different between smokers and nonsmokers with an excess of G to T transversions in smoking-associated cancers. The prevalence of G to T transversions is 30% in smokers' lung cancer but only 12% in lung cancers of nonsmokers. A similar trend exists, albeit less marked, in laryngeal cancers and in head and neck cancers. This type of mutation is infrequent in most other tumors aside from hepatocellular carcinoma. At several p53 mutational hotspots common to all cancers, such as codons 248 and 273, a large fraction of the mutations are G to T events in lung cancers but are almost exclusively G to A transitions in non-tobacco-related cancers. Two important classes of tobacco smoke carcinogens are the polycyclic aromatic hydrocarbons (PAH) and the nicotine-derived nitrosamines. Recent studies have indicated that there is a strong coincidence of G to T transversion hotspots in lung cancers and sites of preferential formation of PAH adducts along the p53 gene. Endogenously methylated CpG dinucleotides are the preferred sites for G to T transversions, accounting for more than 50% of such mutations in lung tumors. The same dinucleotide, when present within CpGmethylated mutational reporter genes, is the target of G to T transversion hotspots in cells exposed to the model PAH compound benzo[a]pyrene-7,8-diol-9,10-epoxide. As summarized here, a number of other tobacco smoke carcinogens also can cause G to T transversion mutations. The available data suggest that p53 mutations in lung cancers can be attributed to direct DNA damage from cigarette smoke carcinogens rather than to selection of pre-existing endogenous mutations.

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Section: Adduct Structuresmentioning

confidence: 99%

Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers

et al. 2002

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“…Initial studies using this approach found BP adducted bases (e.g. BP-6 N7Gua) in the urine of three of seven cigarette smokers and three of seven women exposed to coal smoke, but none were detected in urine from 13 control subjects (Casale et al, 2001).…”

Section: Chemically Unstable Dna Adductsmentioning

confidence: 99%

DNA adduct burden and tobacco carcinogenesis

Wiencke

2002

Oncogene

148

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DNA adducts associated with tobacco smoking could provide a marker of biologically effective dose of tobacco carcinogens and improve individual cancer risk prediction. A significant number of clinical and epidemiologic studies have reported associations of increased DNA adduct levels with the occurrence of the prevalent tobacco related cancers including cancer of the lung, head and neck, and bladder. The inducibility of DNA adducts following in vitro treatments using blood lymphocytes also appears to be a risk factor in the development of lung and head and neck cancer. Corroborative evidence pointing to the importance of DNA adducts in tobacco carcinogenesis include numerous studies showing associations of tobacco smoke exposure with the induction of DNA adducts in humans in vivo. Further effort is necessary, however, to more fully characterize the dose -response relationship between smoking and DNA adducts in exposed target and surrogate tissues. The relationship between gene polymorphisms thought to modify tobacco-related cancer risk and DNA adduct levels is complex. Results of some DNA adduct studies (both in vitro and in vivo) appear inconsistent with the epidemiologic findings. This is evident for polymorphisms involving both carcinogen metabolism (e.g. GSTP1) and DNA repair (e.g. XRCC1). Molecular studies of human tumors suggest associations of p53 mutation with DNA adducts and have revealed correlations of DNA adduct levels with somatic alterations (e.g. 3p21 LOH) that are thought to occur at the very earliest stages of tobacco carcinogenesis. More research is needed to assess the relationship between endogenous sources of DNA adducts and tobacco smoke exposure and the relative oncogenic effects of chemically stable versus unstable DNA adducts. Many potentially fruitful new avenues of cancer research are emerging that integrate DNA adduct analyses with assessments of smoking, genetics, diet and ambient air quality. These investigations aim to understand the multifactorial nature of interindividual variability in response to tobacco carcinogens. As these trends continue a variety of innovative study designs and approaches will become important in human populations.

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“…15,16 Thus we explored the possible association of polymorphisms in XPD and XRCC1 genes with the presence of BPDE-DNA adducts in lymphocytes from lung cancer patients, all active smokers, prototype of subjects heavily exposed to tobacco-derived BP.…”

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confidence: 99%

Effect of dna repair gene polymorphisms on BPDE‐DNA adducts in human lymphocytes

Pastorelli

Cerri

Mezzetti

et al. 2002

Intl Journal of Cancer

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To determine whether variations in DNA repair genes are related to host DNA damage, we investigated the association between polymorphism in the XPD gene (codon 199, 312, 751) and the XRCC1 gene (codon 194, 399) and the presence of benzo(a)pyrene diolepoxide adducts to lymphocyte DNA (BPDE-DNA) in a group of male patients with incident lung cancer, all current smokers. BPDE-DNA adducts were analyzed by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry. XPD and XRCC1 genotypes were identified by PCR-RFLP. XRCC1 and XPD genotypes did not affect the levels and proportion of detectable BPDE-DNA adducts. The patients were also genotyped for the GSTM1 polymorphism, given its role in the detoxification of BPDE. Individuals with the GSTM1 deletion had significantly higher levels of BPDE-DNA adducts when they were XPD-Asp312Asp؉Lys751Lys than carriers of at least one variant allele. No such association was found with the XRCC1 genotypes. Because of the small study population (n ‫؍‬ 60), further statistical analysis of possible gene-gene and geneenvironment would not be informative. This is the first study analysing the specific BPDE-DNA adduct in vivo with regard to polymorphic repair genes (XPD, XRCC1) and xenobiotic metabolizing gene (GSTM1). Our results raise the possibility that the XPD-Asp312Asp؉Lys751Lys genotype may increase BPDE-DNA damage; this effect might be evident in individuals who are especially likely to have accumulated damage, probably because of lower detoxification capacity and high environmental exposure.

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Detection and Quantification of Depurinated Benzo[a]pyrene-Adducted DNA Bases in the Urine of Cigarette Smokers and Women Exposed to Household Coal Smoke

Cited by 66 publications

References 39 publications

Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers

Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers

DNA adduct burden and tobacco carcinogenesis

Effect of dna repair gene polymorphisms on BPDE‐DNA adducts in human lymphocytes

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