DNA fingerprint analysis reveals differences in mutational patterns in experimentally induced rat peritoneal tumors, depending on the type of environmental mutagen

Our plain-English summary of DNA fingerprint analysis reveals differences in mutational patterns in experimentally induced rat peritoneal tumors, depending on the type of environmental mutagen, by N. Kociok, K. Unfried, M. Roller, et al (Cancer Genetics and Cytogenetics, 1999).

The study

• Authors: N. Kociok, K. Unfried, M. Roller, W. Dehnen
• Journal: Cancer Genetics and Cytogenetics
• Published: 1999;111(1):71-6
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We performed tumor DNA fingerprint analysis using the synthetic minisatellite probe S3315x2 based on the 33.15-repeat unit. The aim of the study was to investigate fingerprinting patterns of peritoneal tumors induced experimentally in Wistar rats by two carcinogens with unknown mechanism of action (crocidolite asbestos and nickel powder) and, as a positive control, benzo[a]pyrene. The carcinogens were administered intraperitoneally into rats. The banding patterns obtained with DNA from 71 peritoneal tumors were compared to the corresponding normal tissues. DNA derived from peritoneal tumors induced by the three carcinogens differed with respect to mutation frequencies and mutation patterns. The mutation frequencies in these tumors, revealed by DNA fingerprinting, were 18.2% for benzo[a]pyrene, 14.8% for crocidolite asbestos, and 40.9% for nickel powder. The alterations detected in the banding pattern of benzo[a]pyrene-induced peritoneal tumors were exclusively additional bands. On the contrary, in the DNA from asbestos-induced peritoneal tumors, only deletions of bands were observed on the autoradiographs. In the DNA from nickel-induced peritoneal tumors, both types of mutations occurred. The different mutation frequencies and mutation patterns appear to discriminate between benzo[a]pyrene, crocidolite asbestos, and nickel powder, and may be related to the mechanisms of action of these compounds.

In plain English

In this animal experiment, the authors injected crocidolite asbestos (2 mg), nickel powder (5 mg), benzo[a]pyrene (5 mg, a positive control) or saline into the abdominal cavity of Wistar rats. They compared DNA fingerprint banding patterns of the resulting peritoneal tumors, mostly classified as mesothelioma or malignant fibrous histiocytoma, with normal tissue from the same rat. Mutations were counted in 4 of 27 crocidolite-treated animals with tumors (14.8%), 4 of 22 benzo[a]pyrene-treated animals (18.2%) and 9 of 22 nickel-treated animals (40.9%). The P value for these differences in frequency was 0.08. All changes in the crocidolite tumors were lost bands, and all changes in the benzo[a]pyrene tumors were new bands. The nickel tumors showed both kinds. These pattern differences were statistically significant (P = 0.008). The few tumors in saline-treated controls showed no mutations, but the authors stated that, because of the small numbers, this finding was not statistically significant and was not shown. The authors concluded that the differences may be related to how these substances act. They noted that they could not tell which DNA event caused each band change.

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: Animal experiment: intraperitoneal injection of carcinogens in rats, followed by DNA fingerprint comparison of tumor DNA with normal DNA from the same rat
• Who was studied: Wistar rats with treatment-related peritoneal tumors: 22 benzo[a]pyrene-treated, 22 nickel-treated and 27 crocidolite asbestos-treated animals analyzed. The authors were at Heinrich-Heine-University Düsseldorf, Germany. The dates of the animal work are not given.
• Exposure: Single intraperitoneal doses: crocidolite asbestos 2 mg, nickel powder 5 mg, benzo[a]pyrene 5 mg (positive control). Saline (0.9% NaCl, 2 mL) was the negative control.
• Main results:
  • The tumors were mostly classified as mesothelioma or malignant fibrous histiocytoma, irrespective of the carcinogen used
  • Mutation frequencies: 4 of 22 benzo[a]pyrene-treated animals (18.2%), 9 of 22 nickel-treated animals (40.9% in the table; printed as 40% in the text) and 4 of 27 crocidolite asbestos-treated animals (14.8%)
  • The differences in mutation frequencies between the three carcinogens gave P = 0.08; the authors did not describe these differences as statistically significant
  • In crocidolite asbestos-induced tumors, all mutations were deletions (loss) of a band
  • In benzo[a]pyrene-induced tumors, all mutations were the appearance of a new band
  • In nickel-induced tumors, both types occurred: eight new or intensified bands and three band deletions (11 mutations counted in the pattern analysis)
  • The differences in mutation patterns between the carcinogens were statistically significant (exact Chi-square test, P = 0.008)
  • The few peritoneal tumors in saline-treated controls showed no mutations. Because of small numbers, the authors stated that this finding was not statistically significant, and they did not show it.
• The authors' conclusion: The authors concluded that the different mutation frequencies and patterns may be related to the mechanisms of action of benzo[a]pyrene, crocidolite asbestos and nickel powder
• Limitations the authors state:
  • The method cannot show which molecular event (deletion, insertion or base substitution) caused a band to appear or disappear
  • It could not be determined whether multiple tumors in one animal arose independently or were metastases, so several mutations in one animal were counted as one
  • Changes seen with more than one restriction enzyme could not be separated into independent events and were counted as one mutation
  • DNA must come from tissue that underwent clonal selection, so changes can be seen only at the endpoint
  • Mutations may also arise during tumor growth rather than directly from the carcinogen
  • The saline control finding was based on small numbers, was not statistically significant, and was not shown

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

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

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