Cytogenetic response to asbestos fibers in cultured human primary mesothelial cells from 10 different donors

Our plain-English summary of Cytogenetic response to asbestos fibers in cultured human primary mesothelial cells from 10 different donors, by K. Pelin, A. Hirvonen, M. Taavitsainen, et al (Mutation Research, 1995).

The study

• Authors: K. Pelin, A. Hirvonen, M. Taavitsainen, K. Linnainmaa
• Journal: Mutation Research
• Published: 1995;334(2):225-33
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The ability of amosite asbestos fibers to induce chromosomal aberrations in human primary mesothelial cells obtained from pleural effusions of 10 noncancerous patients was investigated. The glutathione S-transferase M1 (GSTM1) genotypes of the patients were determined, since the GSTM1 null genotype has been associated with increased susceptibility to lung cancer and chemically induced cytogenetic damage. Four of the patients represented the GSTM1 null genotype, and six the GSTM1 positive genotype. Successful chromosome aberration analyses were obtained from six cases, three of them with the GSTM1 null genotype. The level of aberrant cells in unexposed cultures ranged from 2.0% to 7.5%. Statistically significant increases (2.3-3.0-fold compared to controls) in the number of aberrant cells were observed in two cases only: in one case treated with 1 microgram/cm2 of amosite, and in another treated with 2 micrograms/cm2 of amosite. Cell cultures from four individuals showed minor or no increases in the numbers of aberrant cells in the doses tested (1 and 2 micrograms/cm2). Chromosome breaks were the major type of aberration. The amosite exposed cells with significantly increased aberrations were from patients with GSTM1 positive genotypes. Two cases that showed no cytogenetic response to asbestos fibers were of the GSTM1 null genotype. Thus, our results suggest that the lack of the GSTM1 gene does not render human mesothelial cells more susceptible to chromosomal damage induced by asbestos. GSTM1 null cells appeared, however, to be more sensitive to the growth inhibitory effects of asbestos than did GSTM1 positive cells. Variation in the cytogenetic response of human primary mesothelial cells to asbestos fibers was observed to exist, but the fibers do not appear to be potent inducers of structural chromosomal aberrations in these cells. It remains to be established whether individual sensitivity to asbestos fibers, due to specific genetic traits, exists.

In plain English

This was a laboratory study. The authors exposed cultured human mesothelial cells, the cells that line the chest and abdominal cavities, to amosite asbestos. The cells came from fluid around the lungs or in the abdomen of 10 patients thought not to have cancer. One of them was later found to have small cell lung cancer. Cultures were treated with 1 or 2 micrograms per square centimetre of a standard amosite sample for 48 hours, and the authors counted chromosome damage. They also tested each donor for the GSTM1 gene, which four donors lacked (the "null" type). Chromosome analysis succeeded for six donors. Statistically significant increases in damaged cells, 2.3- to 3.0-fold over unexposed cells, were seen in two donors, both GSTM1 positive. Two GSTM1-null donors showed virtually no chromosome response. The lower dose slowed cell growth in three GSTM1-null donors. The authors concluded that amosite caused only small or no increases in structural chromosome aberrations, that is, changes to chromosome structure. They also concluded that cells lacking GSTM1 were not more susceptible to that damage but seemed more sensitive to growth inhibition. They noted that this rested on cells from only 10 people.

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 (in vitro) experiment on cultured human primary mesothelial cells, with genotyping of the donors for GSTM1
• Who was studied: Mesothelial cells from pleural or peritoneal fluid of 10 patients presumed noncancerous (Finland). Five donors were male and five female, aged 23 to 88. Four donors were GSTM1 null and six GSTM1 positive. One donor (UPL9) was later found to have small cell lung cancer.
• Exposure: UICC standard reference amosite asbestos at 1 or 2 micrograms per square centimetre for 48 hours. The authors describe the 1 microgram dose as nontoxic and the 2 microgram dose as giving 50% cell survival, based on earlier data in immortalized cells. Unexposed cultures served as controls.
• Main results:
  • Chromosome aberration analysis succeeded for cells from 6 of the 10 donors, 3 of them GSTM1 null.
  • In unexposed control cultures, aberrant cells (including gaps) ranged from 2.0% to 4.2% in five donors and were 7.5% in the sixth (PL83).
  • Statistically significant increases in aberrant cells were seen in only two donors: PL102 at 1 microgram per square centimetre and UPL8 at 2 micrograms per square centimetre.
  • Those two significant increases were 2.3- to 3.0-fold compared with each donor's controls. Increases in the other donors were less than two-fold.
  • In donor PL83 (GSTM1 null), the increase in aberrant cells at 2 micrograms per square centimetre was close to, but did not reach, statistical significance (P = 0.06).
  • Chromosome breaks (acentric fragments) were the main type of aberration in the three donors with the largest increases.
  • Two donors (UPL29 and PL104), both GSTM1 null, showed virtually no chromosome (cytogenetic) response to amosite. Amosite did, however, inhibit cell proliferation in their cultures.
  • At 1 microgram per square centimetre, amosite inhibited cell proliferation in cells from three donors (UPL29, PL104, UPL9), all GSTM1 null. The same dose appeared to slightly stimulate proliferation in four GSTM1-positive donors.
  • At 2 micrograms per square centimetre, amosite clearly inhibited proliferation of cells from nine donors. Cells from one donor (UPL11) showed increased mitotic activity.
  • The authors stated that cells from different persons differed clearly in their toxic and chromosome-damaging response to asbestos.
• The authors' conclusion: The authors concluded that amosite caused only small or no increases in structural chromosome aberrations. They also concluded that cells lacking the GSTM1 gene were not more susceptible to this damage but seemed more sensitive to the growth-inhibiting effects of asbestos.
• Limitations the authors state:
  • The growth findings by GSTM1 type were based on cells from only 10 individuals.
  • The illnesses that caused the donors' fluid build-up may have contributed to background chromosome abnormalities.
  • Mesothelial cells cannot be obtained from healthy individuals.
  • It is unknown whether cells taken from the same person at different times would respond in a predictable way.
  • For two donors (UPL3 and UPL11), control cultures had too few dividing cells, so their control level of aberrations is unknown.
  • One donor presumed noncancerous (UPL9) turned out to have small cell lung cancer. No chromosome results were obtained from this donor.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Amosite, Pleural Effusion, Glutathione (GSH), Lung Cancer.

Related studies

• Cytotoxicity of oxidants and asbestos fibers in cultured human mesothelial cells — V.L. Kinnula, K. Aalto, et al. (1994)
• Effects of asbestos and man-made vitreous fibers on cell division in cultured human mesothelial cells in comparison to rodent cells — K. Pelin, P. Kivipensas, et al. (1995)
• Specificity of asbestos-induced chromosomal aberrations in short-term cultured human mesothelial cells — K. Olofsson, J. Mark (1989)
• A comparison of the cytogenetic response to asbestos and glass fibre in Chinese hamster and human cell lines. Demonstration of growth inhibition in primary human fibroblasts — A.M. Sincock, J.D. Delhanty, et al. (1982)
• Cytogenetic and pathogenic effects of long and short amosite asbestos — K. Donaldson, N. Golyasnya (1995)
• Differential responses to growth factors by normal human mesothelial cultures from individual donors — J.F. Lechner, M.A. LaVeck, et al. (1989)

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