P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo\[a\]pyrene in rats

Our plain-English summary of P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats, by K. Unfried, N. Kociok, M. Roller, et al (Experimental and Toxicologic Pathology, 1997).

The study

• Authors: K. Unfried, N. Kociok, M. Roller, J. Friemann, F. Pott, W. Dehnen
• Journal: Experimental and Toxicologic Pathology
• Published: 1997;49(3-4):181-7
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mutation analysis of the tumour suppressor gene p53 in tumours induced in the peritoneal cavity of rats revealed differences in the mutational pattern with regard to the carcinogenic substances applied. In tumours induced by benzo[a]pyrene a considerable amount of p53 mutations resulting in an altered protein structure could be detected. For the development of these tumours an escape from the p53 mediated cell cycle control can be assumed. However, in tumours of the same tumour type induced by crocidolite asbestos no mutations could be observed. Since there were even no spontaneous p53 mutations detectable in this tumour group, it is obvious that in these tumours the escape from cell cycle control does not take place via inactivation of p53. Therefore, it is concluded that the molecular mechanisms of carcinogenesis and tumour development in this tumour type depend on the type of carcinogen applied.

In plain English

In this animal experiment, three groups of 48 Wistar rats each received one abdominal-cavity injection: 2 mg of South African crocidolite asbestos, 5 mg of benzo[a]pyrene (a chemical carcinogen), or salt solution as a control. The researchers tested abdominal tumours from the carcinogen-treated rats, which the authors describe as rat mesothelioma, plus two control-group tumours, for point mutations in the tumour suppressor gene p53. The tumours' microscopic differentiation did not differ between the crocidolite and benzo[a]pyrene groups. The researchers found 8 p53 mutations in tumours from the benzo[a]pyrene group (30 tumours examined) and none in the crocidolite group (24 tumours examined). The authors reported p = 0.006 for this difference by Fisher's exact test. One mutation was found in an ovary carcinoma in a control rat. p53 messenger RNA was detected in all of the 14 benzo[a]pyrene and 9 crocidolite tumours tested. The authors concluded that the lack of p53 mutations seems typical of crocidolite-induced, and possibly fibre-induced, tumour development. They said the mechanisms depend on the carcinogen used. They also stated that their results do not show whether fibres cause mutations.

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 in rats) with laboratory analysis of p53 gene mutations and p53 mRNA in the resulting tumours
• Who was studied: Wistar rats (strain Wi/wu, from Kissleg, Germany) in three treatment groups of 48 rats each (crocidolite, benzo[a]pyrene, salt-solution control). The researchers analysed abdominal-cavity tumours from the carcinogen-treated rats and two spontaneous tumours from control rats. Dates of the experiment are not stated.
• Exposure: A single intraperitoneal injection of 2 mg South African crocidolite asbestos in 2 ml of 0.9% salt solution. The comparison group received 5 mg benzo[a]pyrene in a beeswax/tricaprylin carrier, and the control group received 2 ml of 0.9% salt solution.
• Main results:
  • Tumours from the benzo[a]pyrene group had 8 p53 point mutations, and tumours from the crocidolite group had none. As scanned, Table 1 lists 30 benzo[a]pyrene tumours and 24 crocidolite tumours examined, and gives p = 0.006 versus crocidolite by Fisher's exact test.
  • The p value for the comparison of mutations between the benzo[a]pyrene and crocidolite groups
  • In the control group, one ovary carcinoma had a p53 point mutation. Ovary carcinoma was a tumour type not examined in the crocidolite and benzo[a]pyrene groups.
  • In total, the researchers examined 119 genomic DNA samples from carcinogen-induced tumours, plus two spontaneous tumours from the control group.
  • DNA sequencing confirmed the screening method. Sequencing of 37 DNA fragments that screened negative showed no mutations, and every mutation seen in screening was confirmed by sequencing.
  • Every mutation found changed an amino acid in the p53 protein, except one, which created a stop codon.
  • The researchers measured p53 mRNA in 14 benzo[a]pyrene-induced and 9 crocidolite-induced tumours and detected it in all of them, regardless of the tumour-inducing agent. The text gives amounts of roughly 1 to 100 fmol per microgram of RNA.
  • In tumours with p53 mutations, the mRNA produced carried the mutated sequence.
  • The morphological differentiation of the tumours did not differ between animals treated with the different carcinogens (crocidolite and benzo[a]pyrene).
• The authors' conclusion: The authors concluded that the lack of p53 mutations does not appear to be a feature of mesothelioma as a tumour type. In their view, it appears typical of crocidolite-induced, and possibly fibre-induced, carcinogenesis, and the molecular mechanisms of tumour development depend on the carcinogen applied.
• Limitations the authors state:
  • The authors stated that their results do not allow a statement about whether fibres cause mutations, because p53 may not be the gene that fibres target.
  • Because tumour samples may have contained both cancerous and non-cancerous tissue, the authors could not tell whether two bands at one position meant heterozygosity or mixed DNA.

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, Peritoneal Cavity, Carcinogenic, Carcinogenesis.

Related studies

• Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo[a]pyrene — J. Friemann, M. Varnai, et al. (1996)
• On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: I. Urinary and serum mutagenicity studies with rats — C. Varga, G. Horváth, et al. (1998)
• Benzo[a]pyrene-enhanced mutagenesis by asbestos in the lung of lambda-lacI transgenic rats — P. Loli, J. Topinka, et al. (2004)
• Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos — Z. Ni, Y. Liu, et al. (2000)
• Morphological transformation of Syrian hamster embryo cells induced by mineral fibres and the alleged enhancement of benzo[a]pyrene — S.O. Mikalsen, E. Rivedal, et al. (1988)
• On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: II. Tissue specificity studies using comet assay — C. Varga, G. Horváth, et al. (1999)

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