Modulating factors in the expression of radiation-induced oncogenic transformation

Our plain-English summary of Modulating factors in the expression of radiation-induced oncogenic transformation, by E.J. Hall, T.K. Hei (Environmental Health Perspectives, 1990).

The study

• Authors: E.J. Hall, T.K. Hei
• Journal: Environmental Health Perspectives
• Published: 1990;88:149-55
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitative are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing alpha-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene.

In plain English

This article reviewed laboratory systems in which radiation turns cultured cells cancer-like ("oncogenic transformation"), and factors that raise or lower this effect. The quantitative work it described used Syrian hamster embryo cells or mouse C3H 10T1/2 cells. It described thyroid hormone status as altering transformation and vitamin A analogues (retinoids) as suppressing it. Helium-3 ions are densely ionizing particles used to mimic the alpha particles from radon daughters. With them, transformants per initial cell at risk peaked at a value five times higher than with gamma rays. The article also described an experiment cited to an earlier report by the authors' group. Crocidolite asbestos fibers alone (5 micrograms per mL for 24 hours) gave transformation frequencies indistinguishable from the spontaneous rate. Cells pretreated with crocidolite and then given 0.66 Gy of helium-3 ions showed significantly higher transformation than with radiation alone, and the combined effect appeared greater than the sum of the two. The authors concluded this had implications for a possible interaction of radon and asbestos in the environment. They cautioned that changes in cells in a dish are far removed from a tumor in a person.

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: Review of in vitro (cell culture) oncogenic transformation assays and of factors modifying radiation-induced transformation, summarizing laboratory experiments, some from earlier publications
• Who was studied: Cultured cells: short-term explants of Syrian hamster embryo (SHE) cells or the established mouse cell line C3H 10T1/2; no humans studied
• Exposure: Gamma rays, X-rays and helium-3 ions (simulating radon daughter alpha particles); for asbestos, 24-hour pretreatment with crocidolite fibers at 5 micrograms per mL, alone or combined with 0.66 Gy of helium-3 ions
• Main results:
  • In C3H 10T1/2 cells, crocidolite fibers alone, at concentrations causing only moderate cell killing, gave transformation frequencies indistinguishable from the spontaneous rate
  • Cells pretreated with crocidolite for 24 hours and then irradiated with alpha particles (helium-3 ions) had a significantly higher transformation incidence than cells given radiation alone
  • Transformation appeared supra-additive (more than the sum of the two) when asbestos and high-LET particles were given together
  • For densely ionizing helium-3 ions, transformants per initial cell at risk peaked at a much lower dose than for gamma rays and reached a value five times higher
  • About 0.5 Gy of helium-3 ions produced a level of transformants per initial cell at risk that no dose of gamma rays achieved
  • Citing earlier work, the article stated that under hypothyroid conditions neither X-ray nor benzo(a)pyrene-induced transformations were expressed
  • The article showed suppression of radiation-induced transformation by vitamin A analogues, first reported more than 10 years earlier
  • The oncogenes involved in radiation transformation had not yet been identified; the authors considered chromosome translocation the most likely way radiation would activate an oncogene
• The authors' conclusion: The authors concluded that the apparent supra-additivity of asbestos fibers and high-LET particles has implications for a possible interaction of radon and asbestos in the environment, and possibly for combinations of other environmental pollutants
• Limitations the authors state:
  • Altered morphology of a colony in a Petri dish is far removed from an overt tumor in a human, and the systems' limitations must be appreciated
  • The most quantitative systems (SHE, C3H 10T1/2, 3T3) use fibroblasts rather than epithelial cells and are far removed from real-life human carcinogenesis

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Translocation.

Related studies

• Asbestos, radiation and oncogenic transformation — T.K. Hei, E.J. Hall, et al. (1984)
• Asbestos promotes morphological transformation and elevates expression of a gene family invariably induced by tumor promoters in C3H/10T1/2 cells — C.L. Parfett, R. Pilon, et al. (1996)
• The influence of asbestos dust on the oncogenic transformation of C3H10T 1/2 cells — R.C. Brown, A. Poole, et al. (1983)
• SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis — T. Henzi, W.V. Blum, et al. (2009)
• Ionizing radiation: a risk factor for mesothelioma — J.E. Goodman, M.A. Nascarella, et al. (2009)
• Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database — A. Farioli, M. Ottone, et al. (2016)

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