Induction of ferritin synthesis in human lung epithelial cells treated with crocidolite asbestos

Our plain-English summary of Induction of ferritin synthesis in human lung epithelial cells treated with crocidolite asbestos, by R. Fang, A.E. Aust (Archives of Biochemistry and Biophysics, 1997).

The study

• Authors: R. Fang, A.E. Aust
• Journal: Archives of Biochemistry and Biophysics
• Published: 1997;340(2):369-75
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Crocidolite asbestos is a known human carcinogen containing 27% iron by weight. It has previously been shown that iron was mobilized intracellularly from crocidolite after treatment of human lung epithelial cells (A549) and that the toxicity of the fibers was directly related to how much mobilized iron was in the < 10,000 MW (low-molecular-weight, LMW) fraction [C. C. Chao, L.G. Lund, K. R. Zinn, and A. E. Aust (1994) Arch. Biochem. Biophys. 314, 384-391]. The data here show that iron mobilization from crocidolite began immediately after treatment of the A549 cells and increased linearly with time. However, the synthesis of ferritin, an iron storage protein, did not begin until after 4 h of treatment, reaching a sustained maximum after 12 h. Mobilized iron was preferentially incorporated into the nonferritin-protein fraction up to 7 h after treatment, when the amount of iron mobilized was low and before significant accumulation of newly synthesized ferritin had occurred. This suggested that these cultured cells needed additional iron for synthesis of iron-requiring proteins and that iron mobilized from crocidolite could be utilized directly for this purpose. Subsequent to this, additional mobilized iron was incorporated into newly synthesized ferritin. Even though iron from crocidolite was incorporated into newly synthesized ferritin or into other proteins, the amount of iron from crocidolite in the LMW fraction remained constant during the 24 h. Thus, it appeared that synthesis of ferritin may not have fully protected the cells from the toxic effects of iron mobilized from crocidolite.

In plain English

This laboratory experiment treated cultured human lung epithelial A549 cells with crocidolite asbestos. The authors tracked where iron released from the fibers went inside the cells and whether the cells made more ferritin, an iron-storage protein. At the main dose (printed as 3 mg/cm2; the unit may be garbled), the iron released increased steadily for 24 hours. The rate of ferritin production peaked at 10 hours, at five times the rate in untreated cells. The amount of ferritin began rising after 4 hours, peaked after 12 hours and then stayed constant to 24 hours. At 24 hours, roughly 69% of released iron was in ferritin, 28% in other proteins and 3% in a low-molecular-weight fraction. The amount of iron in that fraction stayed relatively constant from 1 to 24 hours; 3% was its share at 24 hours. The authors concluded that ferritin may have offered some protection, but the iron may be a challenge the cells are not prepared to cope with. They suggested that if this happens in the body, it could lead to DNA damage and cancer.

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 cells
• Who was studied: Human lung epithelial A549 cells, a cell line obtained from the American Type Culture Collection; no people were studied
• Exposure: Crocidolite asbestos supplied by NIEHS/NTP. Some was neutron-activated to make the iron radioactive so it could be traced. The main dose is printed as 3 mg crocidolite/cm2 of cell layer. Other doses were also tested, for periods of up to 24 hours.
• Main results:
  • Total iron released from crocidolite inside the treated cells increased linearly with time up to 24 h
  • In cells treated with 3 mg/cm2 crocidolite, the rate of ferritin synthesis peaked at 10 h, at five times control levels, and returned to near the control rate at 24 h
  • In treated cells, the amount of ferritin began to increase after 4 h, reached a maximum after 12 h, and then remained constant up to 24 h
  • Total protein synthesis did not differ between treated and control cells
  • Iron went into ferritin at 9 pmol Fe per million cells per hour from 1 to 4 h, rising to 58 pmol per million cells per hour from 4 to 24 h
  • Of the iron released in 24 h, approximately 69% was in ferritin
  • Of the iron released in 24 h, approximately 28% was in other (nonferritin) proteins
  • The amount of iron in the low-molecular-weight fraction stayed relatively constant from 1 to 24 h. It was about 3% of the total iron released in 24 h; this percentage is its share at 24 h, not a constant share throughout.
  • When the crocidolite dose was raised from 1 to 3 mg/cm2, the majority of released iron shifted from the nonferritin-protein fraction to the ferritin fraction
  • Adding aminoguanidine, an inhibitor of the enzyme that makes nitric oxide, did not change the total amount of ferritin made after 12 or 24 h of exposure
• The authors' conclusion: The authors concluded that iron released from engulfed crocidolite may be an iron challenge the cells are not prepared to cope with. They wrote that ferritin synthesis may have offered some protection. Their earlier work found that crocidolite toxicity tracked low-molecular-weight iron. On that basis, they wrote that the released iron appeared able to damage cells and, if this happens in the body, could result in DNA and other cellular damage leading to cancer.
• Limitations the authors state:
  • The authors state that it is not known what form of iron is responsible for inducing ferritin synthesis
  • The authors state that the substance(s) responsible for releasing iron from crocidolite inside the cells had not yet been identified

Topics

Medical terms in this study, explained in our Lexicon: Ferritin, Crocidolite, A549 Cells.

Related studies

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• Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells — C.C. Chao, S.H. Park, et al. (1996)
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