Genotoxicity of chemical and physical agents in cultured human tissues and cells

Our plain-English summary of Genotoxicity of chemical and physical agents in cultured human tissues and cells, by A. Weston, S.M. Plummer, R.C. Grafstrom, et al (Food and Chemical Toxicology, 1986).

The study

• Authors: A. Weston, S.M. Plummer, R.C. Grafstrom, B.F. Trump, C.C. Harris
• Journal: Food and Chemical Toxicology
• Published: 1986;24(6-7):675-9
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In vitro model systems have recently been developed to investigate the toxicity of chemical, microbial and physical agents in normal human tissues and cells from many of the major tissue sites of high cancer incidence. Pathobiological endpoints used in these studies include alterations in incorporation rates of precursors into DNA, RNA and protein, in the clonal growth rate of cultured cells and in DNA structure (e.g. single-strand breaks, DNA-protein crosslinks and chemical-DNA adducts) and the induction of differentiation, chromosomal and karyotypic abnormalities, mutations and neoplastic transformation. These systems have been used to study a variety of complex mixtures and individual substances, including cigarette smoke components such as benzo[a]pyrene and N-nitrosamines, formaldehyde, fecapentaenes, asbestos, and nickel and chromium ions. In addition, increasing awareness of the role of oncogenes in human carcinogenesis has led to studies involving transfection experiments with oncogenes and hepatitis B viral genes in normal human cells.

In plain English

This article was a brief essay, a review, by researchers at the US National Cancer Institute's Laboratory of Human Carcinogenesis and collaborators. It described laboratory methods for growing normal human tissues and cells and summarized earlier studies, many from the authors' own laboratory, on how cancer-causing agents damage them. It covered cigarette smoke components such as benzo[a]pyrene and N-nitrosamines, formaldehyde, faecal mutagens called fecapentaenes, asbestos fibres, nickel and chromium ions, and experiments inserting cancer genes into human cells. On asbestos, the essay reported earlier findings in which mesothelial cells grown in the laboratory were 10 to 15 times more sensitive to the toxic effects of asbestos fibres than normal human bronchial epithelial cells and fibroblasts. Microscopy showed that the fibres damaged the plasma (outer) membrane of the cell. Asbestos-treated mesothelial cells showed chromosomal damage and abnormal chromosome numbers, along with an extended lifespan. The article did not name a type of asbestos. Other work it summarized found that human bladder and bronchus tissues from different people varied 55- to 75-fold in activating benzo[a]pyrene. The authors concluded that laboratory models using human tissues and cells are of considerable value to biomedical research.

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 (brief essay) of laboratory studies, largely from the authors' own laboratory, some unpublished
• Who was studied: normal human tissues and cells (e.g. bronchus, colon, oesophagus, bladder, mesothelial cells) grown in laboratory culture, obtained from biopsy, surgery or immediate autopsy; no numbers of donors given
• Exposure: asbestos fibres (type not specified), nickel and chromium ions, plus cigarette smoke components (benzo[a]pyrene, N-nitrosamines), formaldehyde, fecapentaenes, and transfection with oncogenes and hepatitis B virus genes
• Main results:
  • Cited earlier work: mesothelial cells in culture were 10 to 15 times more sensitive to the cytotoxic effects of asbestos fibres than normal human bronchial epithelial cells and fibroblasts
  • Cited earlier work: microscopy showed that asbestos fibres damage the plasma membrane; the mesothelial cell's greater sensitivity may be related to the plasticity of its cytoskeleton
  • Cited earlier work: treating mesothelial cells with asbestos fibres resulted in chromosomal damage and aneuploidy (abnormal chromosome numbers), together with an extended lifespan of the altered cells
  • Cited earlier work: nickel-exposed cultured human bronchial epithelial cells had higher population-doubling potential than unexposed cells
  • Cited earlier work: chromium ions induced DNA-protein crosslinking in human bronchial epithelial cells
  • Cited earlier work: tissues from different individuals varied 55- to 75-fold (bladder and bronchus) in activating benzo[a]pyrene, and 50- to 150-fold in N-nitrosamine metabolites detected as DNA adducts
• The authors' conclusion: The authors concluded that in vitro models using human tissues and cells are of considerable value to current biomedical research.

Topics

Medical terms in this study, explained in our Lexicon: Genotoxicity, DNA adducts, Carcinogenesis.

Related studies

• 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)
• Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human alveolar epithelial cell line A549 — V. Rapisarda, C. Loreto, et al. (2015)
• Studies on the role of oxygen radicals in asbestos-induced cytopathology of cultured human lung mesothelial cells — E.W. Gabrielson, G.M. Rosen, et al. (1986)
• Cyto-genotoxicity of amphibole asbestos fibers in cultured human lung epithelial cell line: role of surface iron — R.K. Srivastava, M. Lohani, et al. (2010)
• Reduction of chrysotile asbestos-induced genotoxicity in human peripheral blood lymphocytes by garlic extract — K. Bhattacharya, S. Yadava, et al. (2004)
• Validity of the Lymphocyte Cytokinesis-Block Micronucleus Assay (L-CBMN) as biomarker for human exposure to chemicals with different modes of action: A synthesis of systematic reviews — M. Kirsch-Volders, M. Fenech, et al. (2018)

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