On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo\[a\]pyrene: I. Urinary and serum mutagenicity studies with rats

Our plain-English summary of On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: I. Urinary and serum mutagenicity studies with rats, by C. Varga, G. Horváth, Z. Pocsai, et al (Cancer Letters, 1998).

The study

• Authors: C. Varga, G. Horváth, Z. Pocsai, V. Timbrell
• Journal: Cancer Letters
• Published: 1998;128(2):165-9
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Recently, there has been concern that ingested asbestos may cause an increase in cancer incidence in populations exposed to fibre-contaminated drinking water. Although animal experiments failed to demonstrate carcinogenicity of the oral asbestos exposure, the high adsorption capacity of the fibres creates the possibility of cocarcinogenic action with adsorbed organics. In a simple in vivo model we demonstrated earlier that UICC crocidolite and anthophyllite asbestos fibres were able to adsorb carcinogen molecules from aqueous solutions. When orally administered, these fibres increased the sister chromatid exchange frequency in bone marrow cells of rats. In the present study we tried to follow the desorption and metabolization processes of carcinogenic benzo[a]pyrene molecules transported by the ingested fibres using the highly sensitive Salmonella/Ames mutagenicity assay. The bacterial test was performed on concentrated serum and urine samples of the treated animals by using the TA98 and 100 strains in the presence and absence of liver microsomal and deconjugating enzymes. All sets of urine and serum samples failed to show mutagenic activity indicating a lack of both desorption in the serum and the ability of the liver to metabolize. Considering our results, the cytogenetic impact demonstrated earlier in the bone marrow can be explained by a local action of accumulated and transported carcinogen molecules.

In plain English

The same research group had earlier reported that asbestos fibers coated with the carcinogen benzo[a]pyrene (BaP) raised a marker of genetic damage in rat bone marrow. In this animal experiment, the authors gave female F-344 rats, by stomach tube, 10 mg (50 mg/kg body weight) of UICC crocidolite or anthophyllite asbestos, either plain or pre-coated with BaP. There were three rats per group and six untreated controls. Three other rats received BaP alone at 20 mg/kg as a positive control. Blood serum and 24-hour urine were tested in the Ames bacterial test, which detects substances that cause mutations. The test used strains TA98 and TA100, with and without added liver and deconjugating enzymes. Neither serum nor urine from the asbestos-exposed rats showed mutagenic activity, whether or not the fibers carried BaP. Urine from the positive control rats was mutagenic only when both enzyme sets were added. Their serum was not mutagenic. The authors concluded that the results support the possibility that BaP travels on fiber surfaces in the blood without being released, and is activated in the target tissues themselves.

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 (rats given asbestos by stomach tube; serum and urine tested in the Salmonella/Ames mutagenicity assay)
• Who was studied: Female F-344 inbred rats (about 200 g each), housed individually in metabolism cages. There were three rats in each of four asbestos groups and six untreated controls, plus a positive control group of three rats given BaP and an aqueous-BaP control group. The study was conducted at University Medical School, Debrecen, Hungary.
• Exposure: UICC standard reference crocidolite and anthophyllite asbestos, 10 mg per animal (50 mg/kg body weight) by gavage. Fibers were given either after shaking in distilled water or after pre-coating with BaP from an aqueous solution, making four groups: crocidolite, crocidolite plus BaP, anthophyllite and anthophyllite plus BaP. Positive control rats received BaP at 20 mg/kg body weight dissolved in DMSO.
• Main results:
  • Serum from the asbestos-exposed rats (plain or BaP-coated fibers) showed no mutagenic activity in Salmonella strains TA98 or TA100. Adding liver (S9) and deconjugating enzymes did not change this.
  • Concentrated urine from the asbestos-exposed rats had no significant effect on mutation frequency. BaP pre-coating of the fibers and enzymatic deconjugation did not change the results.
  • In the positive control rats given BaP alone, serum was not mutagenic but urine was. The urine's mutagenicity depended on the presence of both S9 mix and deconjugating enzymes.
  • For positive control urine with S9 and deconjugating enzymes, the mean revertant number (plus or minus SD) was 126 plus or minus 4.2 in strain TA98 (P less than 0.01) and 253 plus or minus 13.4 in strain TA100 (P less than 0.05).
  • Serum and urine from rats given aqueous BaP alone were not mutagenic. The data were not shown.
• The authors' conclusion: The authors concluded that the negative urine results support the possibility that BaP molecules are carried on the fiber surface in the circulating blood without being released. In that case, metabolic activation would take place in the target tissues themselves, which would explain the bone marrow effects they had reported earlier as a local action.
• Limitations the authors state:
  • The authors noted that the negative serum results could reflect either a lack of BaP release from the fibers or a short half-life of any reactive metabolites produced.
  • The authors noted that bone marrow is not considered a real target of asbestos or BaP, so the combined effect may be more pronounced in other tissues not studied here.

Topics

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

Medical terms in this study, explained in our Lexicon: Amphibole Asbestos, Asbestos Exposure, UICC, Crocidolite, Anthophyllite, Carcinogenic.

Related studies

• 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)
• Benzo[a]pyrene-enhanced mutagenesis by asbestos in the lung of lambda-lacI transgenic rats — P. Loli, J. Topinka, et al. (2004)
• P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats — K. Unfried, N. Kociok, et al. (1997)
• 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)
• Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats — J. Topinka, P. Loli, et al. (2006)
• Effect of particulates on metabolism and mutagenicity of benzo[a]pyrene — D.R. Bevan, W.E. Manger (1985)

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