Crocidolite asbestos suppresses the differentiation of HL-60 cells induced by DMSO

Our plain-English summary of Crocidolite asbestos suppresses the differentiation of HL-60 cells induced by DMSO, by A. Ueki, H. Tsushima, F. Hyodoh, et al (Cancer Letters, 1992).

The study

• Authors: A. Ueki, H. Tsushima, F. Hyodoh, K. Kinugawa, M. Tomita, J. Kazahaya, R. Shirato
• Journal: Cancer Letters
• Published: 1992;62(3):225-32
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This study was undertaken to determine if the biological function of inducers for cell differentiation is affected by asbestos fibers, which are sometimes deposited in human tissues. Protein kinase C activity, c-myc protein expression and cell surface CR3 expression were used as the markers of cell differentiation. The function of dimethylsulfoxide (DMSO), an inducer of cell differentiation, was suppressed by the co-culturing of crocidolite asbestos, because DMSO reacted with the hydroxyl radical released after the stimulation with crocidolite and spent itself. Superoxide dismutase (SOD) inhibited the effect of crocidolite, reacting rapidly with .O2- before the secondary release of .OH. Asbestos fibers deposited in tissues may inhibit the function of inducers which stimulate immature cells to differentiate, because such inducers frequently are also radical scavengers.

In plain English

This was a laboratory experiment on cells grown in dishes, not a study of people or animals. The authors used HL-60, a human promyelocytic cell line that the chemical DMSO can make mature into myeloid cells. They asked whether crocidolite asbestos (a UICC standard reference sample) interferes with this maturation. Cells were treated with 1.25% DMSO, with or without crocidolite, and sometimes with the enzyme superoxide dismutase (SOD). With DMSO alone, cytosolic activity of protein kinase C, an enzyme used as a maturation marker, rose more than threefold within 3 days. With crocidolite added, its activity fell between control and DMSO-only levels. Adding SOD brought it back almost to the DMSO-only level. Crocidolite also significantly reduced the share of cells carrying the maturation marker CR3. It raised the share of cells positive for c-myc protein from about 65% to about 88%. Hydroxyl radicals were detected when the cells were stimulated with crocidolite. The authors speculated that DMSO was used up neutralizing these radicals, and noted that the mechanism remained to be clarified. They suggested that asbestos deposited in tissues may inhibit such maturation-inducing agents.

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) cell culture experiment
• Who was studied: Cultured cells of the human promyelocytic cell line HL-60, studied at Kawasaki Medical School, Kurashiki, Japan; no human subjects
• Exposure: Autoclaved crocidolite asbestos (UICC standard reference sample) at 25, 50, 100 or 200 per ml (the unit is printed as 'pg/ml' in the scanned text), with or without 1.25% DMSO; some cultures also received SOD at 50 to 400 U/ml
• Main results:
  • In HL-60 cells given 1.25% DMSO, cytosolic protein kinase C activity (per mg protein) increased more than three times in 3 days
  • In cells given both DMSO and crocidolite, protein kinase C activity fell between that of control cells and that of DMSO-only cells
  • When SOD was added together with DMSO and crocidolite, protein kinase C activity rose to almost the DMSO-only level
  • Adding crocidolite at 25 or 50 to cells being induced with 1.25% DMSO significantly decreased the percentage of CR3-positive cells
  • After 4 days of DMSO, about 65% of cells were positive for c-myc protein
  • When crocidolite (50) was added together with DMSO, c-myc protein-positive cells increased to about 88% of total cells
  • Hydroxyl radical generation was detected when HL-60 cells were stimulated with crocidolite
  • The crocidolite-induced radical signal (DMPO-OH) was markedly decreased in the presence of SOD
  • Neither crocidolite at 50 nor 1.25% DMSO was cytotoxic to the cells
  • LDH release did not differ significantly between cells given DMSO alone and cells given DMSO plus crocidolite
• The authors' conclusion: The authors concluded that asbestos fibers deposited in tissues may inhibit the function of agents that stimulate immature cells to mature, because such agents are often also radical scavengers. They speculated that DMSO was used up neutralizing the hydroxyl radicals stimulated by crocidolite.
• Limitations the authors state:
  • The authors stated that the mechanisms of inhibition remain to be clarified

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Hydroxyl Radical, Superoxide.

Related studies

• Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A — F. Hyodoh, A. Takata-Tomokuni, et al. (2005)
• Characterization of the state of differentiation of six newly established human non-small-cell lung cancer cell lines — G. Bepler, A. Koehler, et al. (1988)
• Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos — H.N. Kim, Y. Morimoto, et al. (2001)
• Enhanced generation of free radicals from phagocytes induced by mineral dusts — V. Vallyathan, J.F. Mega, et al. (1992)
• 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)
• Crocidolite induces prostaglandin I(2) release mediated by vitronectin receptor and cyclooxygenase-2 in lung cells — F.J. Leyva, K. Roberts (2010)

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