3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido\[1,2-α\]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers

Our plain-English summary of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers, by S. Bonassi, F. Cellai, A. Munnia, et al (Toxicology Letters, 2017).

The study

• Authors: S. Bonassi, F. Cellai, A. Munnia, D. Ugolini, A. Cristaudo, M. Neri, M. Milić, A. Bonotti, R.W. Giese, M.E. Peluso
• Journal: Toxicology Letters
• Published: 2017;270:1-7
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20-40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber. We have conducted a mechanistic study to evaluate the association between 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and lipid peroxidation, and asbestos exposure in the peripheral blood of 327 subjects living in Tuscany and Liguria, Italy, stratified by occupational exposure to asbestos. Adduct frequency was significantly greater into exposed subjects with respect to the controls. M1dG per 108 normal nucleotides were 4.0±0.5 (SE) in 156 asbestos workers, employed in mechanic, naval, petrochemical, building industries, and in pottery and ceramic plants, versus a value of 2.3±0.1 (SE) in 171 controls (p<0.001). After stratification for occupational history, the effects persisted in 54 current asbestos workers, mainly employed in building renovation industry (2.9±0.3 (SE)), and in 102 former asbestos workers (4.5±0.7 (SE)), with p-values of 0.033, and <0.001, respectively. A significant effect of smoking on heavy smokers was found (p=0.005). Our study gives additional support to the oxidative stress theory, where M1dG may reflect an additional potential mechanism of asbestos-induced toxicity.

Copyright © 2017 Elsevier B.V. All rights reserved.

In plain English

This cross-sectional study measured M1dG adducts, a form of DNA damage used as a biomarker of oxidative stress and lipid peroxidation, in blood from 327 men. Of these, 156 were asbestos workers from a health-surveillance program in Tuscany, Italy, employed mostly in mechanic, naval and petrochemical industries, but also building, pottery and ceramics. The other 171 were volunteer controls from Liguria. It did not identify the fiber types these workers were exposed to. Asbestos workers averaged 4.0 ± 0.5 (SE) adducts per 10^8 normal nucleotides, versus 2.3 ± 0.1 (SE) in controls (p less than 0.001). Former workers (102) averaged 4.5 ± 0.7 and current workers (54, mainly building renovation) 2.9 ± 0.3. Within each smoking group, former workers remained significantly higher than controls, but current workers did not. Heavy smokers (12 men, over 40 pack-years) averaged 7.2 ± 2.4, versus 2.7 ± 0.2 in non-smokers. The authors concluded that the results support the idea that asbestos damages cells through an oxidative mechanism. They noted possible co-exposures to other carcinogens, possible recall bias, and the lack of a dose-response analysis.

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: Cross-sectional biomarker study comparing DNA adduct levels in blood of asbestos-exposed male workers and male controls
• Who was studied: 327 men, mean age 55.2 years. 156 asbestos workers were enrolled from an occupational medicine health-surveillance program in Tuscany, Italy: 102 former workers and 54 current workers, the current workers mainly in building renovation. 171 controls were volunteers from the Liguria region with no history of jobs involving asbestos or other known or suspected carcinogens. 21% of workers and 19% of controls were current smokers.
• Exposure: Occupational asbestos exposure, assessed from job title and narrative work history in questionnaires. Jobs were mostly in mechanic, naval and petrochemical industries, plus building, pottery and ceramic plants. The article does not state which fiber types this study's workers were exposed to; it mentions chrysotile only when discussing other research. The article reports a mean of 11.5 ± 8.1 (SD) years of asbestos exposure. Smoking (including pack-years) and environmental tobacco smoke were also examined.
• Main results:
  • M1dG adducts per 10^8 normal nucleotides were 4.0 ± 0.5 (SE) in the 156 asbestos workers versus 2.3 ± 0.1 (SE) in the 171 controls (p less than 0.001), after adjusting for confounding factors.
  • The 54 current asbestos workers averaged 2.9 ± 0.3, compared with 2.3 ± 0.1 in controls (p=0.033).
  • The 102 former asbestos workers averaged 4.5 ± 0.7, compared with controls (p less than 0.001).
  • When analyzed by smoking status, former asbestos workers remained significantly higher than controls among non-smokers (p=0.007), ex-smokers (p=0.017) and current smokers (p=0.016).
  • When analyzed by smoking status, current asbestos workers showed no difference from controls (p=0.589, 0.701 and 0.120 in non-smokers, ex-smokers and smokers).
  • Across the whole study population, current and former smokers did not differ significantly from non-smokers. Heavy smokers (more than 40 pack-years, 12 people) averaged 7.2 ± 2.4 (SE), versus 2.7 ± 0.2 (SE) in non-smokers (p=0.005).
  • Among non-smoking asbestos workers, adduct levels tended to rise with years of exposure and then level off (p for trend = 0.004). No individual duration group differed significantly from controls, and no association with duration was seen in former or current smokers.
  • No significant interaction between smoking and asbestos was found. Among former asbestos workers, adducts were 67% higher in current smokers than in non-smokers; among current asbestos workers, smokers were 36% higher.
• The authors' conclusion: The authors concluded that the study supports the hypothesis that asbestos fibers damage cells through an oxidative mechanism, and that M1dG adducts may reflect an additional mechanism of asbestos-induced toxicity.
• Limitations the authors state:
  • No dose-response analysis was performed.
  • Retrospective exposure assessment in former workers may be misleading because of recall bias.
  • Exposure assessment in current workers may be unreliable because asbestos exposure is banned in Italy.
  • Workers may have been co-exposed to other respiratory carcinogens, such as crystalline silica, heavy metals, volatile organic compounds and polycyclic aromatic hydrocarbons.
  • Smoking effects may not have been fully detected because there were few heavy smokers.
  • Only a single type of DNA adduct was analyzed.
  • Findings may be influenced by the use of peripheral blood, which contains a mixture of mostly short-lived cell types.
  • The 32P-postlabeling method cannot determine the precise adduct structure unless it is combined with appropriate standards or mass spectrometry.

Topics

Medical terms in this study, explained in our Lexicon: Silicate, Asbestos Exposure, Pulmonary Fibrosis, Mesothelioma, Latency, Carcinogenic, Oxidative Stress, Reactive Oxygen Species (ROS).

Related studies

• 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 — B. Marczynski, T. Kraus, et al. (2000)
• 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis — A. Valavanidis, T. Vlachogianni, et al. (2009)
• 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)
• Fibre-induced lipid peroxidation leads to DNA adduct formation in Salmonella typhimurium TA104 and rat lung fibroblasts — P.J. Howden, S.P. Faux (1996)
• 8-Hydroxy-2'-deoxyguanosine as a marker of oxidative DNA damage related to occupational and environmental exposures — A. Pilger, H.W. Rüdiger (2006)
• Chromatographic Detection of 8-Hydroxy-2'-Deoxyguanosine in Leukocytes of Asbestos Exposed Workers for Assessing Past and Recent Carcinogen Exposures — F. Cellai, S. Bonassi, et al. (2020)

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