Detection of DNA Adducts in Skin Biopsies of Coal Tar-Treated Psoriasis Patients: Immunofluorescence and &lt;sup&gt;32&lt;/sup&gt;P Postlabeling

Zhang, Yu Jing; Li, You; DeLeo, Vincent A.; Santella, Regina M.

doi:10.1159/000210867

Cited by 16 publications

(9 citation statements)

References 25 publications

(35 reference statements)

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“…Interestingly, rat liver microsomal metabolism of 9-fluoro-BaP gives both trans-7,8-dihydro-7,8-dihydroxy-9-fluoro-BaP and trans-4,5-dihydro-4,5-dihydroxy-9-fluoro-BaP suggesting the 7,8 bond as a possible target for the second oxidation step of 9-hydroxy-BaP (39). Studies are underway to explore the Human/Polish coke oven workers (2) 15.3 Human/aluminum smelter workers (1) 1.48-3.08 Human/psoriasis patients treated with coal tar (6) 0. 18-9.4 Human/cigarette smokers (5) Human/roofers (4) 0.…”

Section: Discussionmentioning

confidence: 99%

“…Industrial populations exposed to processes such as aluminum smelters (1), coke ovens (2), iron and steel foundries (3), and roofing (4), and populations exposed to cigarette smoke (5) and genotoxic agents have been studied (6). In all of these studies, peripheral blood lymphocytes (PBLs) have be used as the accessible target tissue in which to measure the formation of DNA adducts.…”

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confidence: 99%

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Quantitative and Temporal Relationships between DNA Adduct Formation in Target and Surrogate Tissues: Implications for Biomonitoring

Nesnow¹,

Ross²,

Nelson³

et al. 1993

Environmental Health Perspectives

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DNA-carcinogen adducts offer a potential dosimeter for environmental genotoxicants reaching the exposed individual. Because the target tissues for many chemical carcinogens are not readily accessible for monitoring adducts in humans, peripheral blood lymphocytes (PBLs) have served as surrogate sources of exposed DNA. Both benzo[a]pyrene (BaP) and benzo [b]fluoranthene (BbF) are widely distributed in the environment as components of complex mixtures, such as automobile exhaust, cigarette smoke, foods, water, and urban air. Thus, human exposure to these chemicals is widespread, and they probably contribute to overall human lung cancer risk. The interpretation of the results of such studies would be enhanced by an understanding of the pharmacokinetics of specific DNA adduct formation and persistence in both target and surrogate tissues. Polycyclic aromatic hydrocarbons (PAHs) were administered to male Sprague-Dawley rats IP at 100 mg PAH/ kg body weight. Lung, liver, and PBL tissues were harvested 1,3, 7,14, 28, and 56 days after treatment. DNA was extracted from each tissue and 32P-postlabeling analysis of DNA adducts with nuclease P1 enhancement was conducted. In all three tissues, BaP-DNA adducts exhibit a similar pattern, reaching a maximum at 34 days, followed by a decrease to 56 days. For BbF, the maximum DNA adduct levels in each tissue were between 5 and 14 days after injection. By 56 days after administration, the total adducts remaining in all tissues were measurable. Correlation analyses ofthe amount of DNA adducts in lung or liver compared to those found in the PBL of the same animals suggest a range of correlations (R2 = 0.67-0.83). For BaP, DNA adducts in both liver and lung may be predicted by PBL DNA adduct levels. For BbF, adduct levels in PBLs directly reflect adduct levels in the liver and are less predictive of lung adduct levels. The collateral pharmacokinetics for DNA adduct persistence in lung, liver, and PBLs suggest that PBL adduct-based dosimetry may reflect patterns of adduction in other less accessible tissues. Thus, PBL DNA adducts may prove to be useful dosimeters for the delivered dose of DNA.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Quantitative and Temporal Relationships between DNA Adduct Formation in Target and Surrogate Tissues: Implications for Biomonitoring

Nesnow¹,

Ross²,

Nelson³

et al. 1993

Environmental Health Perspectives

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“…Since the advent of sensitive techniques that can measure DNA adducts in human tissues at extremely high levels of sensitivity, there has been numerous papers describing studies on DNA adducts in humans exposed to environmental agents. Industrial populations exposed to processes such as aluminum smelters (1), coke ovens (2), iron and steel foundries (3), and roofing (4), and populations exposed to cigarette smoke (5) and genotoxic agents have been studied (6). In all of these studies, peripheral blood lymphocytes (PBLs) have be used as the accessible target tissue in which to measure the formation of DNA adducts.…”

Section: Introductionmentioning

confidence: 99%

Quantitative and temporal relationships between DNA adduct formation in target and surrogate tissues: implications for biomonitoring.

Nesnow

Ross

Nelson

et al. 1993

Environ Health Perspect

View full text Add to dashboard Cite

DNA-carcinogen adducts offer a potential dosimeter for environmental genotoxicants reaching the exposed individual. Because the target tissues for many chemical carcinogens are not readily accessible for monitoring adducts in humans, peripheral blood lymphocytes (PBLs) have served as surrogate sources of exposed DNA. Both benzo[a]pyrene (BaP) and benzo[b]fluoranthene (BbF) are widely distributed in the environment as components of complex mixtures, such as automobile exhaust, cigarette smoke, foods, water, and urban air. Thus, human exposure to these chemicals is widespread, and they probably contribute to overall human lung cancer risk. The interpretation of the results of such studies would be enhanced by an understanding of the pharmacokinetics of specific DNA adduct formation and persistence in both target and surrogate tissues. Polycyclic aromatic hydrocarbons (PAHs) were administered to male Sprague-Dawley rats IP at 100 mg PAH/kg body weight. Lung, liver, and PBL tissues were harvested 1, 3, 7, 14, 28, and 56 days after treatment. DNA was extracted from each tissue and 32P-postlabeling analysis of DNA adducts with nuclease P1 enhancement was conducted. In all three tissues, BaP-DNA adducts exhibit a similar pattern, reaching a maximum at 3-4 days, followed by a decrease to 56 days. For BbF, the maximum DNA adduct levels in each tissue were between 5 and 14 days after injection. By 56 days after administration, the total adducts remaining in all tissues were measurable. Correlation analyses of the amount of DNA adducts in lung or liver compared to those found in the PBL of the same animals suggest a range of correlations (R2 = 0.67-0.83).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…In the skin, adduct measurement was performed in relation to occupational/medical exposure to PAHs rather than tobacco smoking. For example, in psoriasis patients treated with coal tar, speci®c nuclear staining for ( §)-anti-BPDE-DNA adducts detected by the indirect immuno¯uorescence method was observed in skin biopsies (Zhang et al 1990). The same samples revealed a pattern of multiple DNA adducts in NP1 32 P-postlabelling analyses (Zhang et al 1990).…”

Section: Epidemiological and Biological Data On Pahsmentioning

confidence: 99%

“…For example, in psoriasis patients treated with coal tar, speci®c nuclear staining for ( §)-anti-BPDE-DNA adducts detected by the indirect immuno¯uorescence method was observed in skin biopsies (Zhang et al 1990). The same samples revealed a pattern of multiple DNA adducts in NP1 32 P-postlabelling analyses (Zhang et al 1990). Similar results were also reported by our group in coal tar-treated eczema patients (Godschalk et al 1998).…”

Section: Epidemiological and Biological Data On Pahsmentioning

confidence: 99%

Biomonitoring of tobacco smoke carcinogenicity by dosimetry of DNA adducts and genotyping and phenotyping of biotransformational enzymes: a review on polycyclic aromatic hydrocarbons

2002

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In this review article, we summarize the data on tobacco smoke carcinogenicity in relation to DNA adduct dosimetry and genotyping and phenotyping of biotransformational enzymes. A major class of carcinogens, polycyclic aromatic hydrocarbons, present in substantial quantities in tobacco smoke, is discussed. The historical background and an overview of the metabolic pathways are given. The epidemiological and biological data in particular on dosimetry of the representative DNA adducts and genotyping and phenotyping of the respective activating and detoxifying enzymes are presented. The salient findings are highlighted, the uncertainties are underlined and, finally, recommendations for future research are made.

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Detection of DNA Adducts in Skin Biopsies of Coal Tar-Treated Psoriasis Patients: Immunofluorescence and <sup>32</sup>P Postlabeling

Cited by 16 publications

References 25 publications

Quantitative and Temporal Relationships between DNA Adduct Formation in Target and Surrogate Tissues: Implications for Biomonitoring

Quantitative and Temporal Relationships between DNA Adduct Formation in Target and Surrogate Tissues: Implications for Biomonitoring

Quantitative and temporal relationships between DNA adduct formation in target and surrogate tissues: implications for biomonitoring.

Biomonitoring of tobacco smoke carcinogenicity by dosimetry of DNA adducts and genotyping and phenotyping of biotransformational enzymes: a review on polycyclic aromatic hydrocarbons

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