Xeroderma pigmentosum fibroblasts are more sensitive to asbestos fibers than are normal human fibroblasts

Our plain-English summary of Xeroderma pigmentosum fibroblasts are more sensitive to asbestos fibers than are normal human fibroblasts, by L.L. Yang, R.E. Kouri, R.D. Curren (Carcinogenesis, 1984).

The study

• Authors: L.L. Yang, R.E. Kouri, R.D. Curren
• Journal: Carcinogenesis
• Published: 1984;5(2):291-4
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Xeroderma pigmentosum fibroblasts (XPF) are defective in the repair of certain DNA adducts. We show here that XPF cells are more sensitive to the toxic effects of chrysotile, amosite and crocidolite asbestos than are normal human fibroblasts (NF). XPF cells from different complementation groups have a sensitivity to chrysotile which parallels the degree of their DNA repair deficiency. In addition, the survival of normal cells after chrysotile exposure increases with time if they are kept from replicating, while the survival of XPF cells under the same circumstances does not change.

In plain English

This laboratory study tested asbestos on human fibroblasts (connective-tissue cells) grown in dishes, not on people. It compared fibroblasts from patients with xeroderma pigmentosum, an inherited condition whose cells cannot properly repair certain DNA damage, with normal fibroblasts. Cells were exposed for 72 hours to chrysotile, amosite and crocidolite, and survival was measured by the cells' ability to form colonies. In one xeroderma pigmentosum strain, the dose that reduced survival to 37% was about 0.8 micrograms per millilitre for chrysotile, the most toxic fiber, and 7.0 micrograms per millilitre for crocidolite, the least toxic. Normal cells showed no difference between the fibers. Strains from all four genetic subgroups tested were more sensitive to chrysotile than normal cells. Their sensitivity closely followed how poorly each repairs DNA damage caused by ultraviolet light. When cells were kept from dividing after exposure, this 37% dose rose for normal cells from 80 to 170 micrograms per millilitre over three days. For xeroderma pigmentosum cells it fell from 20 to 11. The authors wrote that their results strongly suggest part of asbestos toxicity to these cells comes from DNA damage that normal cells can repair. They also raised an alternative explanation involving cell membranes.

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: laboratory cell culture experiment (in vitro), published as a short communication
• Who was studied: Human fibroblasts grown in culture. Five xeroderma pigmentosum skin fibroblast strains (XP4LO, XP2BE, XP3NE, XP2RO, XP12BE) came from the American Type Culture Collection or the Human Genetic Mutant Cell Repository. Normal fibroblast cultures came from the American Type Culture Collection or were established by the authors from human bronchus tissue; they included foreskin-derived and bronchus-derived lines. Work was done at Microbiological Associates, Bethesda, MD, USA.
• Exposure: UICC standard reference samples of amosite, crocidolite and Canadian chrysotile, suspended in phosphate buffered saline and autoclaved, then added to the cells at specific concentrations for a 72-hour exposure period
• Main results:
  • In the xeroderma pigmentosum strain XP4LO (complementation group A), chrysotile was the most toxic fiber. The dose resulting in 37% survival (D37) was about 0.8 micrograms per ml. Survival was measured by the cells' ability to form colonies (cloning efficiency).
  • In XP4LO cells, crocidolite was the least toxic fiber, with a D37 of 7.0 micrograms per ml.
  • In normal fibroblasts, no difference in toxicity was seen between chrysotile, amosite and crocidolite. Two additional normal lines (one foreskin-derived, one bronchus-derived) gave virtually identical results.
  • For chrysotile, the steep part of the XP4LO survival curve was 20 times steeper than the normal fibroblast curve.
  • Cells from all four xeroderma pigmentosum complementation groups tested had lower survival than normal fibroblasts after chrysotile exposure.
  • Sensitivity to chrysotile closely followed each strain's degree of deficiency in repairing ultraviolet-light-induced DNA damage, as previously reported. Group A strains (XP4LO, XP12BE), with less than 5% normal repair capacity, were most sensitive. The group C strain (XP2BE, 10-20%) had a survival curve similar to group A. The group D strain (XP3NE, 25-50%) was moderately sensitive. The group E strain (XP2RO, 40-60%) was least sensitive.
  • Normal fibroblasts were kept from dividing after a three-day chrysotile exposure. Their D37 rose from 80 micrograms chrysotile per ml, measured immediately after exposure, to 170 micrograms per ml after an additional three days.
  • Xeroderma pigmentosum cells held the same way were more sensitive at all time periods, and their survival did not increase. Their D37 was 20 micrograms chrysotile per ml on day 3 and 11 micrograms per ml on day 6. The cloning efficiency of unexposed control xeroderma pigmentosum cells did not change (range 9.2-10%).
• The authors' conclusion: The authors concluded that their results strongly suggest, rather than demonstrate, that at least a portion of the toxicity of asbestos to human fibroblasts results from a type of DNA damage that normal fibroblasts can repair but xeroderma pigmentosum fibroblasts cannot.
• Limitations the authors state:
  • The authors noted that numerous fibers stayed attached to the dish and to the cells after the asbestos-containing medium was replaced.
  • The authors, in unpublished work, had been unable to detect asbestos-induced DNA damage directly by conventional biochemical assays, and others had reported the same. They offered possible reasons for this.
  • The authors raised an alternative explanation: asbestos toxicity may come from interaction with a cellular component, such as membranes, that is physically or mechanistically linked to part of the DNA repair system, rather than from direct DNA damage.

Topics

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

Medical terms in this study, explained in our Lexicon: Fibroblast, DNA adducts, Chrysotile, Amosite, Crocidolite.

Related studies

• Morphological transformation in vitro of normal human fibroblasts by chrysotile — L.B. Joseph, R.E. Stephens, et al. (1983)
• Effects of chrysotile co-exposure on BaP binding in normal human fibroblasts — M.J. Chang, N.P. Singh, et al. (1983)
• Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos? — E.R. Kisin, A.R. Murray, et al. (2011)
• Thymidine incorporation by lung fibroblasts as a sensitive assay for biological activity of asbestos — I. Lemaire, D. Gingras, et al. (1982)
• Phosphatide composition of normal, hyperplastic and malignant squamous epithelium — C. Carruthers (1966)
• Cellular ingestion, toxic effects, and lesions observed in human bronchial epithelial tissue and cells cultured with asbestos and glass fibers — A. Haugen, P.W. Schafer, et al. (1982)

Browse more research in Carcinogenesis, or return to medical research.