Performance of short-term tests for detection of human carcinogens

Our plain-English summary of Performance of short-term tests for detection of human carcinogens, by T. Kuroki, T. Matsushima (Mutagenesis, 1987).

The study

• Authors: T. Kuroki, T. Matsushima
• Journal: Mutagenesis
• Published: 1987;2(1):33-7
• Type of article: Review
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The performance of short-term tests for detection of carcinogens has been validated by several investigators and international collaborative programmes. A large number of chemicals have been tested by the Salmonella/microsome assay and high values of sensitivity and specificity, often greater than 70%, were reported. For 71 human carcinogens classified in Groups 1, 2A and 2B by the International Agency for Research on Cancer (IARC), the Salmonella/microsome test showed a sensitivity of 62.1%: 36 were positive out of 58 chemicals tested. Similar or rather higher values were obtained with Escherichia coli mutation assay (72.0%, 18/25), mutation assays in fungi (78.9%, 30/38), mutation assays in insects (65.7%, 23/35), and assays measuring DNA damage in prokaryotes (80.5%, 33/41). In assays using mammalian cells, tests on chromosomal anomaly showed a relatively high sensitivity: 61.7% (29/47) in chromosomal structural aberration assays and 80.6% (25/31) in sister chromatid exchange (SCE) assays. Comparable values were also obtained in mutation assays of mammalian cells (73.0%, 27/37) and cell transformation assays (87.5%, 21/24). Results of monitoring of exposed populations did not necessarily show a high sensitivity to human carcinogens (44.4%, 12/27). Human carcinogen data were further analysed in order to find a combination of tests which may increase the predictive value. Among human carcinogens, 17 chemicals are not mutagenic in the Salmonella/microsome assay. Although 9 of 17 chemicals (asbestos, hormones, chlorinated compounds and 1,4-dioxane) were not positive in any short-term assays, some gave positive results in a variety of assays, e.g. arsenic and benzene were positive in assays of chromosomal anomaly in mammalian cells in vitro. Combinations of the Salmonella/microsome assay with certain tests using mammalian cells were found to increase the sensitivity significantly. Chromosomal anomaly assays of mammalian cells in vitro seem to be most relevant for detection of human carcinogens when used in combination with the Salmonella/microsome assay.

In plain English

This review, first written as a working paper for a 1985 IARC workshop, examined how well laboratory tests identify chemicals that cause cancer. It summarized studies by other researchers and added the authors' own analysis of published data on 71 agents in IARC Groups 1, 2A and 2B. IARC rates Group 1 agents carcinogenic to humans and Group 2 agents probably carcinogenic, with higher (2A) or lower (2B) evidence. The Salmonella/microsome assay was positive for 36 of 58 agents tested (62.1%). Chromosomal aberration assays in mammalian cells in vitro gave 61.7% (29/47), and cell transformation assays, excluding the BHK-21 assay, 87.5% (21/24). Of 17 agents not mutagenic in the Salmonella assay, nine, including asbestos, were not positive in the other assays tabulated. The authors wrote that asbestos is carcinogenic to animals and humans but not mutagenic to prokaryotes or eukaryotes. For agents tested by both the Salmonella assay and one of five mammalian-cell tests, combined sensitivities were 83.9 to 95.5%. The authors concluded that chromosomal anomaly assays in mammalian cells in vitro seem most relevant alongside the Salmonella assay.

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 short-term (laboratory) carcinogen tests, originally a working paper for an IARC workshop. It summarizes earlier validation studies and adds the authors' own tabulation of published test results for agents in IARC Groups 1, 2A and 2B.
• Who was studied: 71 chemicals or agents in IARC Groups 1, 2A and 2B. Group 1 agents are carcinogenic to humans. Group 2 agents are probably carcinogenic to humans, with higher (2A) or lower (2B) degrees of evidence. Test data were taken from IARC monographs Vol. 1-37, IARC monographs supplement 4, and other published sources.
• Exposure: Asbestos was one of the agents covered and is listed in IARC Group 1. No fiber type is named. The study looked at results of short-term tests for DNA damage, mutation, chromosomal anomalies and cell transformation.
• Main results:
  • For the agents in IARC Groups 1, 2A and 2B, the Salmonella/microsome assay had a sensitivity of 62.1%: 36 of 58 chemicals tested were positive.
  • DNA damage assays in prokaryotes had a sensitivity of 80.5% (33/41).
  • In assays using mammalian cells, chromosomal structural aberration assays had a sensitivity of 61.7% (29/47) and SCE assays 80.6% (25/31). Table IV lists both under mammalian cells in vitro.
  • Mutation assays using mammalian cells had a sensitivity of 73.0% (27/37). Cell transformation assays, excluding the BHK-21 assay, had a sensitivity of 87.5% (21/24).
  • In people exposed mostly through occupation or medical treatment, peripheral blood cells were positive in 48.0% (12/25) for chromosomal aberrations and 54.5% (6/11) for SCE.
  • Of the 17 agents in Groups 1, 2A or 2B that were not mutagenic in the Salmonella/microsome assay, 9 were not positive in the other assays tabulated. These 9 were asbestos, hormones, chlorinated compounds and 1,4-dioxane.
  • Combined sensitivities were calculated only for the chemicals tested by both the Salmonella/microsome assay and a given second test, so each combination covered a different set of chemicals. When the Salmonella/microsome assay was combined with any of five tests using mammalian cells, sensitivity ranged from 83.9 to 95.5%. The authors described this as a significant increase.
• The authors' conclusion: The authors concluded that chromosomal anomaly assays of mammalian cells in vitro seem most relevant for detecting human carcinogens when used in combination with the Salmonella/microsome assay.
• Limitations the authors state:
  • Chemicals have been tested unevenly: some in many assay systems, others in only a few.
  • Human carcinogenicity is difficult to evaluate and is based largely on epidemiological data.
  • Test results in exposed humans do not necessarily reflect human carcinogenicity.
  • Sensitivity values varied with which chemicals were selected for testing.

Topics

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

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