Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats

Our plain-English summary of Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats, by C. Schürkes, W. Brock, J. Abel, et al (Mutation Research, 2004).

The study

• Authors: C. Schürkes, W. Brock, J. Abel, K. Unfried
• Journal: Mutation Research
• Published: 2004;553(1-2):59-65
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhaled fibres with certain physico-chemical properties are known to induce mesothelioma in humans. The induction of reactive oxygen (ROS) or nitrogen species (RNS) have been suggested as molecular mechanism of fibre induced carcinogenesis. In earlier studies we were able to demonstrate that crocidolite asbestos in vivo induces mutations in transgenic rats with a specific molecular spectrum that indicates the involvement of 8-hydroxydeoxyguanosine (8-OHdG) as pre-mutagenic adduct. 8-OHdG may be induced by primary (direct) and/or secondary (cellular mediated) mechanisms. Therefore, the induction of 8-OHdG as well as the inflammatory response of animals treated with fibre samples significantly differing in their physico-chemical characteristics was investigated. As appropriate system to study mesothelioma carcinogenesis, intraperitoneal injection in rats was used with samples of UICC crocidolite, crocidolite with reduced iron content, and a vitreous fibre (MMVF 11). Equal numbers of carcinogenic fibres from each sample revealed significant comparable increases in 8-OHdG induction. Parameters of inflammation (percentage of macrophages and TNF-alpha secretion) correlated significantly with the induction of 8-OHdG, 10 weeks after treatment.

In plain English

This was an animal experiment. Female Wistar rats (10 per group) received an injection into the abdomen of one of three fibre samples: UICC crocidolite asbestos, the same crocidolite pre-treated with iron chelators (which reduced its iron content by approximately 10%), or a man made vitreous fibre, MMVF 11. Control rats received salt solution. Doses were chosen to give equal numbers of carcinogenic fibres (1 mg and 2 mg of crocidolite, 14.7 mg and 29.4 mg of MMVF 11), and higher MMVF 11 doses were also given. After 10 or 20 weeks, the authors measured 8-OHdG, a form of oxidative DNA damage, in the greater omentum. They also measured inflammation in abdominal fluid. 8-OHdG was significantly increased after 10 weeks in the asbestos groups and the matching MMVF 11 groups, and in all treated groups at 20 weeks. Untreated and iron-reduced crocidolite produced 8-OHdG levels of the same order of magnitude. At 10 weeks, the percentage of macrophages correlated with 8-OHdG (r = 0.43, P less than 0.001, 63 animals). At 20 weeks there was no correlation. The authors concluded that their results give indications that fibre-induced inflammation is relevant for the induction of 8-OHdG.

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: animal experiment (intraperitoneal injection of fibres in rats)
• Who was studied: Female Wistar rats, 10 animals per group, injected at 12 weeks of age and killed 10 or 20 weeks after treatment
• Exposure: UICC crocidolite asbestos, crocidolite pre-treated with iron chelators, and the man made vitreous fibre MMVF 11. Doses were 1 mg and 2 mg of each crocidolite sample and 14.7 mg and 29.4 mg of MMVF 11 (equal carcinogenic fibre numbers). Further MMVF 11 doses of 50 mg and 100 mg were also given.
• Main results:
  • Pre-treatment of crocidolite with iron chelators reduced its iron content by about 10%.
  • At 10 weeks, 8-OHdG in the greater omentum was significantly increased in asbestos-treated rats and in rats given the corresponding MMVF 11 doses.
  • At 20 weeks, 8-OHdG levels were significantly increased in all treated groups.
  • At 20 weeks, inflammation in asbestos-treated rats remained in the same range, but their 8-OHdG levels were significantly reduced compared with 10 weeks.
  • Untreated UICC crocidolite and iron-reduced crocidolite induced 8-OHdG to the same order of magnitude.
  • The authors did not observe a dose-dependent effect on 8-OHdG overall.
  • The higher MMVF 11 dose groups (chosen by carcinogenic potency) showed a dose-dependent increase in 8-OHdG after 20 weeks.
  • At 10 weeks, the low MMVF 11 dose (14.7 mg) significantly increased the percentage of macrophages, while the 100 mg dose decreased it.
  • TNF-alpha secretion and macrophage numbers correlated significantly in individual animals.
  • Macrophage percentage correlated with 8-OHdG at 10 weeks (63 animals, r = 0.43, P less than 0.001) but not at 20 weeks (53 animals, r = -0.05, P greater than 0.5).
  • No malignant transformation of the diaphragm's mesothelial cell layer was observed, so no animals were excluded.
• The authors' conclusion: The authors concluded that their results give indications that fibre-induced inflammation is relevant for the induction of 8-OHdG.
• Limitations the authors state:
  • The authors noted that the delayed response of the high-dose MMVF 11 groups disturbed the correlation between inflammation and 8-OHdG.
  • The authors said their proposed explanation, based on fibre biopersistence, should be investigated with repeated measurements over long observation periods.

Topics

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

Medical terms in this study, explained in our Lexicon: Vitreous, Crocidolite, Mesothelioma, Carcinogenesis, 8-OHdG, UICC, Carcinogenic, Inflammation.

Related studies

• Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos — H. Fung, Y.W. Kow, et al. (1997)
• Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos — R. Yamaguchi, T. Hirano, et al. (1999)
• Iron-dependent formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA102 induced by crocidolite — S.P. Faux, P.J. Howden, et al. (1994)
• Glutathione modulates the formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres — P.J. Howden, S.P. Faux (1996)
• P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats — K. Unfried, N. Kociok, et al. (1997)
• Bromo-deoxyuridine (BRDU) uptake in the lungs of rats inhaling amosite asbestos or vitreous fibres at equal airborne fibre concentrations — K. Donaldson, D.M. Brown, et al. (1995)

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