Biological monitoring among coke oven workers

Haugen, Aage; Benestad, Christel; Vähäkangas, Kirsi; Trivers, Glennwood E.; Harris, Curtis C.

doi:10.1016/0277-5379(85)90388-8

European Journal of Cancer and Clinical Oncology

1985

DOI: 10.1016/0277-5379(85)90388-8

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Biological monitoring among coke oven workers

Aage Haugen¹,

Christel Benestad²,

Kirsi Vähäkangas³

et al.

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Cited by 10 publications

(15 citation statements)

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“…4D) The data are consistent with growing evidence for damage to human DNA by BP and other environmental carcinogens (29,30). Previously SFS has been used to detect BPDE-DNA adducts in peripheral leukocytes from coke oven workers (23,25,26). In some studies, corroborative enzyme immunoassays have also provided evidence for the presence of BPDE-DNA adducts in industrially exposed individuals (23,26).…”

supporting

confidence: 76%

“…This technique is highly sensitive and specific for analysis of relatively simple mixtures of fluorescent compounds, especially PAHs. SFS is described in detail elsewhere (14,16) and has previously been used to assay for BPDE-DNA adducts in humans (23,26). Two types of SFS analysis were used for these studies: simple two-dimensional SFS with a Perkin-Elmer MPF-66 fluorescence spectrophotometer (Perkin-Elmer, Rockville, MD) with a fixed wavelength difference of 34 nm and three-dimensional SFS, where a total of 30 synchronous spectra were generated for each sample in a Perkin-Elmer 650-40 fluorescence spectrophotometer by incrementing the fixed wavelength difference by 4 nm beginning at 10 nm and finishing at 126 nm.…”

mentioning

confidence: 99%

“…Previously SFS has been used to detect BPDE-DNA adducts in peripheral leukocytes from coke oven workers (23,25,26). In some studies, corroborative enzyme immunoassays have also provided evidence for the presence of BPDE-DNA adducts in industrially exposed individuals (23,26). Evidence for BPDE-DNA adducts in human placenta has previously been equivocal.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Detection of benzo[a]pyrene diol epoxide-DNA adducts in human placenta.

Manchester

Weston

Choi

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Human placenta is a readily available organ that responds to maternal environmental insult and has been previously used to investigate metabolism and bioactivation of procarcinogens, for example, benzo[alpyrene. HPLC in com-bination with synchronous fluorescence spectroscopy was used to examine 28 placentas for the presence of benzo[a]pyrene diol epoxide-DNA adducts, and 10 of these were found to be positive. DNA samples from these placentas were subsequently pooled and subjected to partial enzymatic digestion to oligonucleotide fragments. Concentration of those DNA fragments containing benzo[alpyrene diol epoxide-DNA adducts was achieved by immunoaffinity chromatography with polyclonal antibodies raised against these adducts. Column eluates were hydrolyzed under mild acid conditions and extracted with an organic solvent. The presence of benzo[a]pyrene-7,10/8,9-tetrahydrotetrol residues in the extracts was determined by HPLC and synchronous fluorescence spectroscopy and was confirmed by GC/MS. The results unequivocally confirm bioactivation and formation of DNA adducts from benzo[ajpyrene in human placenta in vivo and establish a methodological approach to direct measurement of carcinogen-DNA adducts that are formed as a result of human environmental exposure.

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supporting

confidence: 76%

mentioning

confidence: 99%

See 1 more Smart Citation

Detection of benzo[a]pyrene diol epoxide-DNA adducts in human placenta.

Manchester

Weston

Choi

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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“…BP carcinogenesis could be initiated by the formation of DNA adducts through covalent bonding of its active metabolites to DNA bases. One of the metabolic pathways of BP involves one‐electron oxidation to generate radical cations that can react with N‐7 or C‐8 of guanine or with N‐3 or N‐7 of adenine, to form DNA adducts 3–7. These adducts can be depurinated from the DNA backbone to form apurinic sites, and excreted in urine 8.…”

mentioning

confidence: 99%

Analysis of N7‐(benzo[a]pyrene‐6‐yl)guanine in urine using two‐step solid‐phase extraction and isotope dilution with liquid chromatography/tandem mass spectrometry

Chen¹,

Wang²,

Wu³

2005

Rapid Comm Mass Spectrometry

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Analysis of urinary N7-(benzo[a]pyren-6-yl)guanine (BP-6-N7Gua), a DNA adduct induced by benzo[a]pyrene, may serve as a risk-associated biomarker for exposure to polyaromatic hydrocarbons (PAHs). In this study a highly sensitive and specific analytical method, incorporating on-line sample preparation coupled with isotope-dilution liquid chromatography and tandem mass spectrometry (LC/MS/MS), was developed to quantitate this adduct in human urine. In order to achieve accurate quantitation, 15N5-labeled BP-6-N7Gua was synthesized to serve as the internal standard, and a two-step solid-phase extraction (SPE) procedure using C8 and SCX cartridges was used for sample cleanup. BP-6-7-N7Gua was analyzed using positive ion LC/MS/MS operated in multiple reaction monitoring (MRM) mode. The [M+H]+ ions at m/z 402 and 407 and the common fragment ion of [M+H]+ at m/z 252 were monitored for quantification. The recovery of this analyte after two-step SPE was 90%, and the limit of detection was 2.5 fmol/mL in 10 mL of urine. This highly specific and sensitive method for BP-6-N7Gua in urine may be applied to assess exposure to PAHs in coke-oven workers for future molecular epidemiology studies on health effects of PAHs.

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“…Sensitive assays have been developed to assess exposure to BAP by measuring DNA adducts in human blood lymphocytes that have included immunoassays, synchronous fluorescence spectroscopy, fluorescence-HPLC, and [32P]-postlabeling (15)(16)(17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

Chronic, topical exposure to benzo[a]pyrene induces relatively high steady-state levels of DNA adducts in target tissues and alters kinetics of adduct loss.

Talaska

Jaeger

Reilman

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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Carcinogen-DNA adduct measurements may become useful biomarkers of effective dose and/or early effect. However, validation of this biomarker is required at several levels to ensure that human exposure and response are accurately reflected. Important Adduct levels increased with increasing dose, but the slope of the dose-response was different in each organ. At low doses, accumulation was linear in skin and lung, but at high doses the adduct levels in the lung increased dramatically at the same time when the levels in the skin reached apparent steady state. In the liver adduct, levels were lower than in target tissues and apparent steady-state adduct levels were reached rapidly, the maxima being independent of dose, suggesting that activating metabolism was saturated in this organ. Removal of adducts from skin, the target organ, was more rapid following single treatment than with chronic exposure. This finding is consistent with earlier data, indicating that some areas of the genome are more resistant to repair. Thus, repeated exposure and repair cycles would be more likely to cause an increase in the proportion ofcarcinogen-DNA adducts in repair-resistant areas of the genome. These findings indicate that single-dose experiments may underestimate the potential for carcinogenicity for compounds that follow this pattern.

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Biological monitoring among coke oven workers

Cited by 10 publications

References 0 publications

Detection of benzo[a]pyrene diol epoxide-DNA adducts in human placenta.

Detection of benzo[a]pyrene diol epoxide-DNA adducts in human placenta.

Analysis of N7‐(benzo[a]pyrene‐6‐yl)guanine in urine using two‐step solid‐phase extraction and isotope dilution with liquid chromatography/tandem mass spectrometry

Chronic, topical exposure to benzo[a]pyrene induces relatively high steady-state levels of DNA adducts in target tissues and alters kinetics of adduct loss.

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