Association between 8-hydroxy-2'-deoxyguanosine levels in DNA of workers highly exposed to asbestos and their clinical data, occupational and non-occupational confounding factors, and cancer

Our plain-English summary of Association between 8-hydroxy-2'-deoxyguanosine levels in DNA of workers highly exposed to asbestos and their clinical data, occupational and non-occupational confounding factors, and cancer, by B. Marczynski, T. Kraus, P. Rozynek, et al (Mutation Research, 2000).

The study

• Authors: B. Marczynski, T. Kraus, P. Rozynek, H.J. Raithel, X. Baur
• Journal: Mutation Research
• Published: 2000;468(2):203-12
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In the preceding paper [B. Marczynski, P. Rozynek, T. Kraus, St. Schlösser, H.J. Raithel, X. Baur, Levels of 8-hydroxy-2'-deoxyguanosine in DNA of white blood cells from workers highly exposed to asbestos in Germany, Mutat. Res. (2000) submitted] we described significant increases (p<0.001) in the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells (WBC) of workers highly exposed to asbestos fibers at the workplace relative to those found in the control group in all three study years (period between 1994 and 1997). The results show that the oxidative DNA damage in exposed individuals is between 1.7 times and twice that found in control samples for all 3 years of the study (p<0.001). The aim of this study was to examine the association between the 8-OHdG levels in WBC DNA of workers highly exposed to asbestos fibers at the workplace and clinical data, occupational and non-occupational confounding factors, and cancer. There is no obvious correlation between the steady-state levels of 8-OHdG in the circulating WBC DNA of asbestos workers and possible confounding factors, such as the presence of benign asbestos-associated diseases, the duration of asbestos exposure, the latency period, the fixed cumulative fibrous dust dose ("fiber years"), age, smoking status, acute febrile infections, medicines, aspirin, calcium (Ca(2+)), magnesium (Mg(2+)), and the hormone and vitamin intake. This indicates that previous inhalation of asbestos fibers is the major factor responsible for the difference observed in oxidative DNA damage between asbestos workers and controls. For patients suffering from respiratory cancer, cancer of the gastrointestinal tract, mouth/pharynx/larynx, and urogenital tract the mean DNA-adduct level was significantly higher (p<0.01) than that found in controls, but not significantly higher (p>0.05) than that for asbestos-exposed patients without tumours. The formation of 8-OHdG adduct levels in WBC DNA of patients with hematopoietic cancer, chondrosarcomas and multiform glioblastomas was not significantly higher than that found in the control group (p>0.05). Our results support the hypothesis that oxidative DNA damage in man caused by asbestos fibers plays a role in the formation of malignant tumours.

In plain English

This German study measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, in the white blood cell DNA of workers highly exposed to asbestos in the past. Workers were examined in three study years between 1994 and 1997 (418, 373 and 444 workers) and compared with 214 healthy unexposed controls. The article does not name the asbestos fiber types. The authors found no significant correlation between 8-OHdG levels and benign asbestos-associated diseases, exposure duration, latency, fiber years, age, smoking, infections, medicines or vitamins. There were 43 workers with cancer. For respiratory, gastrointestinal, mouth/pharynx/larynx and urogenital cancers, mean levels were significantly higher than in controls, but not significantly higher than in exposed workers without tumours. Workers with lymphomas and certain other cancers did not differ significantly from controls. The authors concluded that their results support the hypothesis that asbestos-caused oxidative DNA damage plays a role in tumour formation. They added that 8-OHdG cannot distinguish exposed people with and without cancer. They noted that the marker was measured in blood cells rather than target cells and that the group was very heterogeneous.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Biomarker study measuring 8-OHdG in white blood cell DNA of formerly asbestos-exposed workers over three study years, comparing subgroups, cancer cases and unexposed controls. Statistical methods included t-tests, Kruskal-Wallis and Mann-Whitney tests and multiple regression.
• Who was studied: Workers in Germany highly exposed to asbestos in the past, examined in 1994–1995 (n=418), 1995–1996 (n=373) and 1996–1997 (n=444). Among them were 43 cancer cases. Controls were 214 healthy adults living in Germany who were not occupationally exposed. Details of the exposed group are given in a preceding paper.
• Exposure: Past occupational asbestos exposure; fiber types are not specified. The mean end of exposure was 1970, and none of the workers were currently exposed. Exposure was analysed by duration (10 years or less up to more than 40 years), latency, and cumulative dose in 'fiber years' (under 25, 25–100, over 100).
• Main results:
  • Among asbestos workers, no significant correlations were found between DNA adduct levels and occupational or non-occupational factors: duration of exposure, latency period, fiber years, age, smoking status, acute febrile infections, medicines, aspirin, calcium, magnesium and/or hormones, and vitamins.
  • No difference in DNA adduct values was found between exposed workers with and without benign asbestos-associated diseases (asbestosis, asbestos-associated pleural plaques).
  • There were 43 cases of cancer in the exposed group.
  • Patients with respiratory, gastrointestinal, mouth/pharynx/larynx and urogenital tract cancers had mean DNA adduct levels significantly higher than controls (p less than 0.01). Their levels were not significantly higher than those of asbestos-exposed workers without tumours (n=507, mean 2.58 plus or minus 0.61, median 2.54 8-OHdG per 10 to the 5th dG; p greater than 0.05). Controls had a mean of 1.52 plus or minus 0.39.
  • By cancer site (mean plus or minus SD, 8-OHdG per 10 to the 5th dG), each significantly different from controls:
• bronchial carcinoma: n=5, 2.87 plus or minus 0.67
• pleural mesothelioma: n=5, 2.31 plus or minus 0.47
• prostate: n=6, 2.27 plus or minus 0.44
• gastrointestinal: n=12, 2.84 plus or minus 1.12
• mouth/pharynx/larynx: n=3, 3.08 plus or minus 0.42
• urinary bladder/kidney: n=3, 3.15 plus or minus 0.77
  • Patients with Hodgkin and non-Hodgkin lymphomas (n=5, mean 1.78 plus or minus 0.41) and other cancers, chondrosarcomas and multiform glioblastomas (n=4, mean 1.98 plus or minus 0.75), did not have levels significantly higher than controls (p greater than 0.05).
  • In 10 exposed persons with cancer examined in all three years, mean levels rose from 2.67 to 2.95 to 3.51. This change was not statistically significant (p greater than 0.05).
• The authors' conclusion: The authors concluded that their results support the hypothesis that oxidative DNA damage caused by asbestos exposure plays a role in the formation of malignant tumours. They also concluded that the 8-OHdG level cannot be used to differentiate between asbestos-exposed individuals with and without cancer.
• Limitations the authors state:
  • 8-OHdG was measured in surrogate cells (white blood cells), not in the target cells.
  • The study group was very heterogeneous in asbestos-associated diseases, age, exposure duration, fiber years, latency and smoking, which the authors give as a possible reason for the lack of correlations.
  • Information on acute infections and intake of medicines and vitamins was not obtained from all subjects.
  • The 8-OHdG level reflects a balance between damage and repair, so it can rise because of reduced repair rather than more damage.
  • About 30% of samples from cancer patients showed no genotoxic effects, so the authors call the value of DNA adduct levels for predicting cancer in an individual questionable.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Confounding, 8-OHdG, Asbestos Exposure, Latency, Fiber Year.

Related studies

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• 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers — S. Bonassi, F. Cellai, et al. (2017)
• Urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and biopyrrins levels among construction workers with asbestos exposure history — R. Yoshida, Y. Ogawa, et al. (2001)
• Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos — Q. Chen, J. Marsh, et al. (1996)
• Determination of carcinogenic potential of mineral fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells — N. Murata-Kamiya, T. Tsutsui, et al. (1997)

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