The genetic toxicity of human carcinogens and its implications

Our plain-English summary of The genetic toxicity of human carcinogens and its implications, by M.D. Shelby (Mutation Research, 1988).

The study

• Author: M.D. Shelby
• Journal: Mutation Research
• Published: 1988;204(1):3-15
• Type of article: Review
• Cited by: 166 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

23 chemicals and chemical combinations have been designated by the International Agency for Research on Cancer (IARC) as causally associated with cancer in humans. The literature was searched for reports of their activity in the Salmonella mutagenicity assay and for evidence of their ability to induce chromosome aberrations or micronuclei in the bone marrow of mice or rats. In addition, the chemical structures of these carcinogens were assessed for the presence of electrophilic substituents that might be associated with their mutagenicity and carcinogenicity. The purpose of this study was to determine which human carcinogens exhibit genetic toxicity in vitro and in vivo and to what extent they can be detected using these two widely employed short-term tests for genetic toxicity. The results of this study revealed 20 of the 23 carcinogens to be active in one or both short-term tests. Treosulphan, for which short-term test results are not available, is predicted to be active based on its structure. The remaining two agents, asbestos and conjugated estrogens, are not mutagenic to Salmonella; asbestos is not likely to induce cytogenetic effects in the bone marrow and the potential activity of conjugated estrogens in the bone marrow is difficult to anticipate. These findings show that genetic toxicity is characteristic of the majority of IARC Group 1 human carcinogens. If these chemicals are considered representative of human carcinogens, then two short-term tests may serve as an effective primary screen for chemicals that present a carcinogenic hazard to humans.

In plain English

This 1988 single-author paper reviewed published test results rather than reporting a new experiment. The author took the 23 chemicals and chemical combinations that the International Agency for Research on Cancer (IARC) had designated as causing cancer in humans, asbestos among them. The author searched the literature for results from two short-term tests of genetic damage: the Salmonella bacterial mutation test, and tests for chromosome damage in the bone marrow of mice or rats. Of 22 carcinogens with results available, 20 were genetically damaging in one or both tests, and 12 in both. For asbestos, the literature showed that several types of asbestos fibers produced no effect in the Salmonella test, and no bone marrow reports were found. Asbestos had been reported to cause chromosome damage in cultured mammalian cells, but the author did not expect it to reach or affect bone marrow. Judged by these two tests, asbestos and perhaps conjugated estrogens would be the only agents not counted as genetically damaging. The author concluded that most known human carcinogens are overtly genotoxic. The author also noted that, because no chemicals had been designated as human non-carcinogens, the tests could not be checked against them.

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 published literature on genetic toxicity test results, combined with an assessment of chemical structures; no new experiments
• Who was studied: The 23 chemicals and chemical combinations designated by IARC (Supplement 4, 1982) as Group 1 human carcinogens, including asbestos
• Exposure: Results reported in the literature for the Salmonella mutagenicity assay and for rodent bone marrow tests for chromosomal aberrations or micronuclei. For asbestos, 'several types of asbestos fibers' were covered; the fiber types are not named in the article.
• Main results:
  • Of 22 human carcinogens with Salmonella and/or rodent bone marrow results available, 20 were genotoxic in one or both tests, and 12 were positive in both.
  • Asbestos: the reviewed literature (Chamberlain and Tarmy, 1977) reported that several types of asbestos fibers produced no effect in the Salmonella assay.
  • Asbestos: no reports of bone marrow cytogenetic effects were found. Asbestos had been reported (per IARC Supplement 4) to induce chromosomal aberrations in cultured mammalian cells.
  • Given its physical characteristics and localized carcinogenic effects, the author did not expect asbestos to reach or induce effects in the bone marrow.
  • As defined by the two assays, asbestos and perhaps conjugated estrogens would be the only nongenotoxins among the 23 carcinogens.
  • In a table drawn from IARC Supplement 4 and Wilbourn et al. (1986), asbestos was listed with tumor sites of lung and pleura in test animals and lung, larynx and pleura in humans. It was marked as having common tumor sites in animals and humans.
• The authors' conclusion: The author concluded that the majority of known human carcinogens are overtly genotoxic. The author also concluded that the genetic toxicity of nearly all of them can be detected using only the Salmonella test and a rodent bone marrow test for micronuclei or chromosomal aberrations.
• Limitations the authors state:
  • The ability of these short-term tests to tell human carcinogens from non-carcinogens could not be assessed, because no chemicals had been designated as human non-carcinogens.

Topics

Medical terms in this study, explained in our Lexicon: IARC, Micronuclei, IARC Classification, Carcinogenic.

Related studies

• A human cell system for detecting asbestos cytogenotoxicity in vitro — T. Takeuchi, M. Nakajima, et al. (1999)
• Implications of multiple mechanisms of carcinogenesis for short-term testing — B.L. Harper, D.L. Morris (1984)
• Asbestos fibers are mutagenic after all: new signs of orthodoxy for a paradoxical group of carcinogens — T.M. Fasy (1991)
• Performance of short-term tests for detection of human carcinogens — T. Kuroki, T. Matsushima (1987)
• Peculiarities of the clastogenic properties of chrysotile-asbestos fibers and zeolite particles — A.D. Durnev, N.O. Daugel-Dauge, et al. (1993)
• The utility of the in vitro micronucleus test for evaluating the genotoxicity of natural and manmade nano-scale fibres — P. Fowler, A. Homan, et al. (2016)

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